Journal articles: 'Septin 4'

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Shinoda, Tomoyasu, Hidenori Ito, Kaori Sudo, Ikuko Iwamoto, Rika Morishita, and Koh-ichi Nagata. "Septin 14 Is Involved in Cortical Neuronal Migration via Interaction with Septin 4." Molecular Biology of the Cell 21, no. 8 (April 15, 2010): 1324–34. http://dx.doi.org/10.1091/mbc.e09-10-0869.

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Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.

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Onishi, Masayuki, Takako Koga, Aiko Hirata, Taro Nakamura, Haruhiko Asakawa, Chikashi Shimoda, Jürg Bähler, et al. "Role of Septins in the Orientation of Forespore Membrane Extension during Sporulation in Fission Yeast." Molecular and Cellular Biology 30, no. 8 (February 1, 2010): 2057–74. http://dx.doi.org/10.1128/mcb.01529-09.

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ABSTRACT During yeast sporulation, a forespore membrane (FSM) initiates at each spindle-pole body and extends to form the spore envelope. We used Schizosaccharomyces pombe to investigate the role of septins during this process. During the prior conjugation of haploid cells, the four vegetatively expressed septins (Spn1, Spn2, Spn3, and Spn4) coassemble at the fusion site and are necessary for its normal morphogenesis. Sporulation involves a different set of four septins (Spn2, Spn5, Spn6, and the atypical Spn7) that does not include the core subunits of the vegetative septin complex. The four sporulation septins form a complex in vitro and colocalize interdependently to a ring-shaped structure along each FSM, and septin mutations result in disoriented FSM extension. The septins and the leading-edge proteins appear to function in parallel to orient FSM extension. Spn2 and Spn7 bind to phosphatidylinositol 4-phosphate [PtdIns(4)P] in vitro, and PtdIns(4)P is enriched in the FSMs, suggesting that septins bind to the FSMs via this lipid. Cells expressing a mutant Spn2 protein unable to bind PtdIns(4)P still form extended septin structures, but these structures fail to associate with the FSMs, which are frequently disoriented. Thus, septins appear to form a scaffold that helps to guide the oriented extension of the FSM.

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Tsang, Christopher W., Mathew P. Estey, Jessica E. DiCiccio, Hong Xie, Dana Patterson, and William S. Trimble. "Characterization of presynaptic septin complexes in mammalian hippocampal neurons." Biological Chemistry 392, no. 8-9 (August 1, 2011): 739–49. http://dx.doi.org/10.1515/bc.2011.077.

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Abstract Septins are GTPases that form heteromeric complexes and are linked to neurological disorders. Although several septin subcomplexes have been reported in various mammalian tissues, the cellular and subcellular distribution of these complexes is largely unexplored. Using antibodies against ten mammalian septins, we show that septins diverge with respect to their tissue distribution implying that septin complexes in various tissues have unique composition. Although all ten septins examined were expressed in brain tissue, we describe septin complex(es) including SEPT3, SEPT5, SEPT6, SEPT7 and SEPT11 that could be functional within the presynapse because, unlike other septins they: (1) showed an increase in expression from embryonic day 15 to post-natal day 70, (2) were abundantly expressed in axons and growth cones of developing hippocampal neurons, (3) were found in presynaptic terminals of mature synapses, (4) were enriched in a preparation of synaptic vesicles and (5) immunoprecipitated together from brain tissue and cultured nerve cells. Knockdown of SEPT5 or SEPT7 in developing hippocampal neurons impaired axon growth. Because septins are functionally linked to the cytoskeleton and vesicle traffic, presynaptic neuronal septin complexes could be important for ensuring proper axon development and neurotransmitter release.

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An, Hanbing, Jennifer L. Morrell, Jennifer L. Jennings, Andrew J. Link, and Kathleen L. Gould. "Requirements of Fission Yeast Septins for Complex Formation, Localization, and Function." Molecular Biology of the Cell 15, no. 12 (December 2004): 5551–64. http://dx.doi.org/10.1091/mbc.e04-07-0640.

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Septins are GTP binding proteins important for cytokinesis in many eukaryotes. The Schizosaccaromyces pombe genome sequence predicts orthologues of four of five Saccharomyces cerevisiae septins involved in cytokinesis and these are named Spns1-4p. That spns1-4 are not essential genes permitted the application of a combined genetic and proteomics approach to determine their functional relationships. Our findings indicate that Spns1-4p are present throughout interphase as a diffusely localized ∼8.5S complex containing two copies of each septin linked together as a chain in the order Spn3p-Spn4p-Spn1p-Spn2p. Septin recruitment to the medial region of the cell is genetically separable from ring formation, and whereas it is normally restricted to mitosis, it can be promoted without activation of the mitotic cell cycle machinery. Coalescence into ring structures requires Spn1p and Spn4p associate with at least one other septin subunit and the expression of Mid2p that is normally restricted to mitosis. This study establishes the functional requirements for septin complex organization in vivo.

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Fliegauf, Manfred, Anja Kahle, Karsten Häffner, and Barbara Zieger. "Distinct localization of septin proteins to ciliary sub-compartments in airway epithelial cells." Biological Chemistry 395, no. 2 (February 1, 2014): 151–56. http://dx.doi.org/10.1515/hsz-2013-0252.

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Abstract Mucociliary clearance of the airways is accomplished by cilia-mediated laminar mucus flow along the planar epithelial surface. Maintenance of the highly specific architecture of the ciliated airway epithelium with columnar-shaped epithelial cells and tightening of the epithelial barrier is mainly attributed to the F-actin cytoskeleton. Recently, members of the highly conserved family of septin proteins have been shown to play crucial roles in ciliated tissue. These GTP-binding proteins form hetero-oligomeric complexes and assemble higher-order cytoskeletal structures such as filaments, bundles and ring-like structures such as a membrane diffusion barrier at the ciliary base. Here we analyzed the subcellular and sub-ciliary localization of various septin proteins by immunofluorescence imaging of airway epithelial cells. In addition to cytoplasmic localization we found that septins are either enriched at the apical cell cortex including the ciliary bases (septin-2, -4, -6, and -7), or show axonemal staining (septin-2, -7, -9 and -11) or specifically localize to ciliary sub-compartments (septin-8 and -9). The distinct localization of septins suggests structural functions as cytoskeletal components and as elements of the mechanical barrier at the apical cell cortex. Furthermore, the tight association of septin-8 and -9 with the ciliary compartment indicates a possible involvement in cilia-specific functions and cilia-related diseases.

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Shinoda, Tomoyasu, Hidenori Ito, Kaori Sudo, Ikuko Iwamoto, Rika Morishita, and Koh-ichi Nagata. "Septin 14 is involved in cortical neuronal migration via interaction with Septin 4." Neuroscience Research 68 (January 2010): e251. http://dx.doi.org/10.1016/j.neures.2010.07.1113.

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Casamayor, Antonio, and Michael Snyder. "Molecular Dissection of a Yeast Septin: Distinct Domains Are Required for Septin Interaction, Localization, and Function." Molecular and Cellular Biology 23, no. 8 (April 15, 2003): 2762–77. http://dx.doi.org/10.1128/mcb.23.8.2762-2777.2003.

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ABSTRACT The septins are a family of cytoskeletal proteins present in animal and fungal cells. They were first identified for their essential role in cytokinesis, but more recently, they have been found to play an important role in many cellular processes, including bud site selection, chitin deposition, cell compartmentalization, and exocytosis. Septin proteins self-associate into filamentous structures that, in yeast cells, form a cortical ring at the mother bud neck. Members of the septin family share common structural domains: a GTPase domain in the central region of the protein, a stretch of basic residues at the amino terminus, and a predicted coiled-coil domain at the carboxy terminus. We have studied the role of each domain in the Saccharomyces cerevisiae septin Cdc11 and found that the three domains are responsible for distinct and sometimes overlapping functions. All three domains are important for proper localization and function in cytokinesis and morphogenesis. The basic region was found to bind the phosphoinositides phosphatidylinositol 4-phosphate and phosphatidylinositol 5-phosphate. The coiled-coil domain is important for interaction with Cdc3 and Bem4. The GTPase domain is involved in Cdc11-septin interaction and targeting to the mother bud neck. Surprisingly, GTP binding appears to be dispensable for Cdc11 function, localization, and lipid binding. Thus, we find that septins are multifunctional proteins with specific domains involved in distinct molecular interactions required for assembly, localization, and function within the cell.

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Rios-Valencia, Diana G., Edgar O. López-Villegas, Dylan Diaz Chiguer, Adrian Marquez Navarro, Ruben D. Díaz-Martín, Benjamin Nogueda-Torres, and Javier R. Ambrosio. "In Vitro Analyses Reveal the Effect of Synthetic Cytokinin Forchlorfenuron (FCF) on a Septin-Like Protein of Taeniid Cysticerci." Journal of Parasitology Research 2019 (March 3, 2019): 1–11. http://dx.doi.org/10.1155/2019/8578936.

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Cytokinin forchlorfenuron (FCF), a synthetic cytokinin, has been used specifically for the characterization of septins. In spite of genomic evidence of their existence, nothing is known about septin filaments in taeniid cestodes. The aim of this work was to determine the presence of a septin-like protein in cysticerci of Taenia crassiceps and Taenia solium using the deduced amino acid sequence of T. solium septin 4 (SEPT4_Tsm), to design and synthesize a derived immunogenic peptide (residues 88 to 103), to prepare a specific rabbit polyclonal antibody, and to examine the effects of FCF at different concentrations and exposure times on an in vitro culture of T. crassiceps cysticerci. In vitro, FCF altered the morphology and motility of T. crassiceps cysticerci, and its effects were reversible under specific concentrations. In addition, we observed by ultrastructural observation that FCF alters the cellular subunit of the protonephridial system of cestodes, where disruption of the axoneme pattern of flame cells was observed. The rabbit polyclonal antibody prepared against the synthetic peptide recognized a major band of 41 kDa in both parasites. Our results establish the importance of SEPT4_Tsm in the dynamics and survival of taeniid cysticerci, as well as their susceptibility to FCF. This is also the first report that a septin is present in the cytoskeleton of taeniids.

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Wasik, Anita A., Zydrune Polianskyte-Prause, Meng-Qiu Dong, Andrey S. Shaw, John R. Yates, Marilyn G. Farquhar, and Sanna Lehtonen. "Septin 7 forms a complex with CD2AP and nephrin and regulates glucose transporter trafficking." Molecular Biology of the Cell 23, no. 17 (September 2012): 3370–79. http://dx.doi.org/10.1091/mbc.e11-12-1010.

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Podocytes are insulin-sensitive and take up glucose in response to insulin. This requires nephrin, which interacts with vesicle-associated membrane protein 2 (VAMP2) on GLUT4 storage vesicles (GSVs) and facilitates their fusion with the plasma membrane. In this paper, we show that the filament-forming GTPase septin 7 is expressed in podocytes and associates with CD2-associated protein (CD2AP) and nephrin, both essential for glomerular ultrafiltration. In addition, septin 7 coimmunoprecipitates with VAMP2. Subcellular fractionation of cultured podocytes revealed that septin 7 is found in both cytoplasmic and membrane fractions, and immunofluorescence microscopy showed that septin 7 is expressed in a filamentous pattern and is also found on vesicles and the plasma membrane. The filamentous localization of septin 7 depends on CD2AP and intact actin organization. A 2-deoxy-d-glucose uptake assay indicates that depletion of septin 7 by small interfering RNA or alteration of septin assembly by forchlorfenuron facilitates glucose uptake into cells and further, knockdown of septin 7 increased the interaction of VAMP2 with nephrin and syntaxin 4. The data indicate that septin 7 hinders GSV trafficking and further, the interaction of septin 7 with nephrin in glomeruli suggests that septin 7 may participate in the regulation of glucose transport in podocytes.

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Valadares, Napoleão Fonseca, Humberto d’ Muniz Pereira, Ana Paula Ulian Araujo, and Richard Charles Garratt. "Septin structure and filament assembly." Biophysical Reviews 9, no. 5 (September 13, 2017): 481–500. http://dx.doi.org/10.1007/s12551-017-0320-4.

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Badrane, Hassan, M. Hong Nguyen, and Cornelius J. Clancy. "Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans." Antimicrobial Agents and Chemotherapy 60, no. 6 (March 28, 2016): 3591–600. http://dx.doi.org/10.1128/aac.02711-15.

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Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] activates the yeast cell wall integrity pathway.Candida albicansexposure to caspofungin results in the rapid redistribution of PI(4,5)P2and septins to plasma membrane foci and subsequent fungicidal effects. We studiedC. albicansPI(4,5)P2and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5)P2and septins were visualized by live imaging ofC. albicanscells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5)P2was also visualized in GFP-PH domain-expressingC. albicans mkc1mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5)P2and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5)P2levels increased in a dose-response manner at caspofungin concentrations of ≤4× MIC and progressively decreased at concentrations of ≥8× MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5)P2and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4× MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5)P2redistribution remained apparent inmkc1mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at ≤4× and ≥8× MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H2O2did not impact the PI(4,5)P2or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5)P2-septin and PKC-Mkc1 responses that correlate with the extent ofC. albicanskilling, and the responses are not induced by other antifungal agents. PI(4,5)P2-septin regulation is crucial in early caspofungin responses and PKC-Mkc1 activation.

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Lyu, Jie-Yu, Jian-Yong Chen, Xiao-Jun Zhang, Meng-Wen Zhang, Geng-Sheng Yu, Liang Zhang, and Zhong Wen. "Septin 9 Methylation in Nasopharyngeal Swabs: A Potential Minimally Invasive Biomarker for the Early Detection of Nasopharyngeal Carcinoma." Disease Markers 2020 (May 5, 2020): 1–7. http://dx.doi.org/10.1155/2020/7253531.

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Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia, and an unfavorable outcome is usually attributed to advanced stage NPC. Current methods for the early diagnosis of NPC have limitations in clinical practice. The aim of this study was to investigate the diagnostic ability of Septin 9 methylation for NPC. A quantitative methylation-sensitive PCR (qMS-PCR) assay was developed to measure the methylation status and levels of Septin 9 in nasopharyngeal tissues and paired swabs from patients with NPC, chronic nasopharyngitis, and healthy donors. Methylated Septin 9 was detected in 92% (23/25) of NPC tissues and 25% (4/16) of nasopharyngitis controls (p<0.05). High-frequency hypermethylation with decreased mRNA expression of Septin 9 in NPC was also identified. Further, Septin 9 methylation was identified in 90.5% (19/21) of NPC biopsies and 71.4% (15/21) of paired swabs, indicating a good concordance between the two sample types. In addition, methylated Septin 9 was found in 16 (72.7%) nasal swabs from 22 NPC patients, 2 of 19 (10.5%) nasopharyngitis, but not in any of the healthy controls (p<0.01). The methylation score in nasal swabs of the NPC group was also significantly higher than that of non-NPC controls (p<0.001). Moreover, receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.882 of Septin 9 methylation tests to discriminate NPC from non-NPC subjects. Our study demonstrated that frequent methylation of Septin 9 was present in NPC. Its detection in nasopharyngeal swabs may provide a minimally invasive and informative method for identifying early NPC cases.

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Spiliotis, Elias T., Stephen J. Hunt, Qicong Hu, Makoto Kinoshita, and W. James Nelson. "Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules." Journal of Cell Biology 180, no. 2 (January 21, 2008): 295–303. http://dx.doi.org/10.1083/jcb.200710039.

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In epithelial cells, polarized growth and maintenance of apical and basolateral plasma membrane domains depend on protein sorting from the trans-Golgi network (TGN) and vesicle delivery to the plasma membrane. Septins are filamentous GTPases required for polarized membrane growth in budding yeast, but whether they function in epithelial polarity is unknown. Here, we show that in epithelial cells septin 2 (SEPT2) fibers colocalize with a subset of microtubule tracks composed of polyglutamylated (polyGlu) tubulin, and that vesicles containing apical or basolateral proteins exit the TGN along these SEPT2/polyGlu microtubule tracks. Tubulin-associated SEPT2 facilitates vesicle transport by maintaining polyGlu microtubule tracks and impeding tubulin binding of microtubule-associated protein 4 (MAP4). Significantly, this regulatory step is required for polarized, columnar-shaped epithelia biogenesis; upon SEPT2 depletion, cells become short and fibroblast-shaped due to intracellular accumulation of apical and basolateral membrane proteins, and loss of vertically oriented polyGlu microtubules. We suggest that septin coupling of the microtubule cytoskeleton to post-Golgi vesicle transport is required for the morphogenesis of polarized epithelia.

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Honorat, Josephe A., A. Sebastian Lopez-Chiriboga, Thomas J. Kryzer, James P. Fryer, Michelle Devine, Angela Flores, Vanda A. Lennon, Sean J. Pittock, and Andrew McKeon. "Autoimmune septin-5 cerebellar ataxia." Neurology - Neuroimmunology Neuroinflammation 5, no. 5 (July 9, 2018): e474. http://dx.doi.org/10.1212/nxi.0000000000000474.

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ObjectiveTo report a form of autoimmune cerebellar ataxia in which antibodies target septin-5, a guanosine triphosphate (GTP)-binding neural protein involved in neurotransmitter exocytosis.MethodsArchived sera and CSF specimens with unclassified synaptic antibodies were re-evaluated by tissue-based indirect immunofluorescence assay. Autoantigens were identified by Western blot and mass spectrometry. Recombinant protein assays (Western blot, cell based, and protein screening array) confirmed antigen specificity.ResultsSerum and CSF from 6 patients produced identical synaptic immunoglobulin G (IgG) staining patterns of synaptic regions (neuropil) of the mouse cerebrum and cerebellum. The molecular layer of the cerebellum and the thalamus demonstrated stronger immunoreactivity than the midbrain, hippocampus, cortex, and basal ganglia. The antigen revealed by mass spectrometry analysis of immunoprecipitated cerebellar proteins and confirmed by recombinant protein assays was septin-5. All 4 patients with records available had subacute onset of cerebellar ataxia with prominent eye movement symptoms (oscillopsia or vertigo). None had cancer detected. Improvements occurred after immunotherapies (2) or spontaneously (1). One patient died.ConclusionSeptin-5 IgG represents a biomarker for a potentially fatal but treatable autoimmune ataxia.

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Okuzaki, Daisuke, and Hiroshi Nojima. "Kcc4 associates with septin proteins of Saccharomyces cerevisiae." FEBS Letters 489, no. 2-3 (January 31, 2001): 197–201. http://dx.doi.org/10.1016/s0014-5793(01)02104-4.

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Jiménez, Javier, Víctor J. Cid, Rosa Cenamor, María Yuste, Gloria Molero, César Nombela, and Miguel Sánchez. "Morphogenesis beyond Cytokinetic Arrest in Saccharomyces cerevisiae." Journal of Cell Biology 143, no. 6 (December 14, 1998): 1617–34. http://dx.doi.org/10.1083/jcb.143.6.1617.

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The budding yeast lyt1 mutation causes cell lysis. We report here that lyt1 is an allele of cdc15, a gene which encodes a protein kinase that functions late in the cell cycle. Neither cdc15-1 nor cdc15-lyt1 strains are able to septate at 37°C, even though they may manage to rebud. Cells lyse after a shmoo-like projection appears at the distal pole of the daughter cell. Actin polarizes towards the distal pole but the septins remain at the mother–daughter neck. This morphogenetic response reflects entry into a new round of the cell cycle: the preference for polarization from the distal pole was lost in bud1 cdc15 double mutants; double cdc15-lyt1 cdc28-4 mutants, defective for START, did not develop apical projections and apical polarization was accompanied by DNA replication. The same phenomena were caused by mutations in the genes CDC14, DBF2, and TEM1, which are functionally related to CDC15. Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant. Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis.

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Martinez, Constantino, Judith A. Dent, Susan Russell, and Jerry Ware. "A Dynamic Regulation of Platelet Secretion by Septin Proteins." Blood 104, no. 11 (November 16, 2004): 3529. http://dx.doi.org/10.1182/blood.v104.11.3529.3529.

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Abstract Septins form a cytosolic protein family gaining recognition as important effectors in molecular mechanisms involving membrane rearrangements, such as cytokinesis and exocytosis. So far, twelve different members of the family (named SEPT1 to SEPT12) have been characterized in mammals, and their roles are not limited to those mentioned above, but embrace a large number of physiological and pathophysiological events. In particular, reports have associated septins with cancer, apoptosis and neurodegenerative diseases. In this study, we further characterize the platelet septin, SEPT5 (formerly CDCrel-1) as a regulator of platelet physiology. SEPT5 is highly expressed in megakaryocytes, heart and brain and is directly linked to secretion mechanisms in both platelets and neurons. In neurons, SEPT5 negatively modulates neurotransmitter release and has recently been implicated in mechanisms leading to development of schizophrenia in rat models. In platelets, we and others have shown that SEPT5 is preferentially located around α-granules and associates with syntaxin 4 and other members of the septin protein family (SEPT4 and SEPT8) to form a cytoplasmic macromolecular complex. Work from other laboratories has linked SEPT5 to different members of the SNARE family such as syntaxin 1A, the sec6/8 complex, and SNAP25. We have found the overexpression of mouse SEPT5 is associated with fewer α-granules but those present are larger in size suggesting levels of Sept5 maintain normal α-granule size. In a murine model of SEPT5 deficiency, platelets display an increased sensitivity to platelet agonists such as collagen and the thromboxane analogue U46619. To date, SEPT5 is the only mammalian septin whose relevance has been tested in a mouse knockout model. Our current studies use a lumi-aggregometer to document the active secretion of ATP in SEPT5 deficient platelets. Platelets lacking SEPT5 are more responsive to submaximal concentrations of acid insoluble fibrillar type I collagen (< 2.5 mg/mL). We observe a 2- to 3-fold increase in ATP secretion in deficient platelets as compared to their wild-type littermates. The increased dense granule release in the absence of SEPT5 also coincides with increased platelet aggregation. A maximum release of ATP was determined in the presence of the calcium ionophore (A23187, 40μM). Higher concentrations of collagen (5 μg/ml) produced a maximum level of ATP release in SEPT5 deficient mice unlike their wild-type littermates. Our current hypothesis places SEPT5 as a scaffolding protein that serves to anchor other proteins into higher-ordered molecular complexes. SEPT5 biology in platelets needs to be further studied to fully understand its role in granule secretion and formation. While important for platelet biology, these studies may also have implications for mechanisms associated with neurotransmitter release. As such, the platelet becomes an excellent model for analyzing SEPT5 function with implications for hemostasis and beyond.

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Káčeriková, Radka, Jana Godočíková, Zhexin Wang, Eva Kutejová, Stefan Raunser, and Marian Farkašovský. "Modulation of septin higher-order structure by the Cdc28 protein kinase." Biologia 73, no. 10 (August 30, 2018): 1025–33. http://dx.doi.org/10.2478/s11756-018-0116-4.

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Park, Chong Jin, Sukgil Song, Philip R. Lee, Wenying Shou, Raymond J. Deshaies, and Kyung S. Lee. "Loss of CDC5 Function in Saccharomyces cerevisiae Leads to Defects in Swe1p Regulation and Bfa1p/Bub2p-Independent Cytokinesis." Genetics 163, no. 1 (January 1, 2003): 21–33. http://dx.doi.org/10.1093/genetics/163.1.21.

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Abstract In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of budding yeast polo kinase Cdc5p, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal domain. Here we show that, at a semipermissive temperature, the cdc5-3 mutant exhibited a synergistic bud elongation and growth defect with loss of HSL1, a component important for normal G2/M transition. Loss of SWE1, which phosphorylates and inactivates the budding yeast Cdk1 homolog Cdc28p, suppressed the cdc5-3 hsl1Δ defect, suggesting that Cdc5p functions at a point upstream of Swe1p. In addition, the cdc5-4 and cdc5-7 mutants exhibited chained cell morphologies with shared cytoplasms between the connected cell bodies, indicating a cytokinetic defect. Close examination of these mutants revealed delayed septin assembly at the incipient bud site and loosely organized septin rings at the mother-bud neck. Components in the mitotic exit network (MEN) play important roles in normal cytokinesis. However, loss of BFA1 or BUB2, negative regulators of the MEN, failed to remedy the cytokinetic defect of these mutants, indicating that Cdc5p promotes cytokinesis independently of Bfa1p and Bub2p. Thus, Cdc5p contributes to the activation of the Swe1p-dependent Cdc28p/Clb pathway, normal septin function, and cytokinesis.

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Baust, Thorsten, Mihaela Anitei, Cornelia Czupalla, Iryna Parshyna, Line Bourel, Christoph Thiele, Eberhard Krause, and Bernard Hoflack. "Protein Networks Supporting AP-3 Function in Targeting Lysosomal Membrane Proteins." Molecular Biology of the Cell 19, no. 5 (May 2008): 1942–51. http://dx.doi.org/10.1091/mbc.e08-02-0110.

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The AP-3 adaptor complex targets selected transmembrane proteins to lysosomes and lysosome-related organelles. We reconstituted its preferred interaction with liposomes containing the ADP ribosylation factor (ARF)-1 guanosine triphosphatase (GTPase), specific cargo tails, and phosphatidylinositol-3 phosphate, and then we performed a proteomic screen to identify new proteins supporting its sorting function. We identified ≈30 proteins belonging to three networks regulating either AP-3 coat assembly or septin polymerization or Rab7-dependent lysosomal transport. RNA interference shows that, among these proteins, the ARF-1 exchange factor brefeldin A-inhibited exchange factor 1, the ARF-1 GTPase-activating protein 1, the Cdc42-interacting Cdc42 effector protein 4, an effector of septin-polymerizing GTPases, and the phosphatidylinositol-3 kinase IIIC3 are key components regulating the targeting of lysosomal membrane proteins to lysosomes in vivo. This analysis reveals that these proteins, together with AP-3, play an essential role in protein sorting at early endosomes, thereby regulating the integrity of these organelles.

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Jeon, Tae-Won, Heebum Yang, Chang Geol Lee, Sang Taek Oh, Daekwan Seo, In Hye Baik, Eun Hye Lee, Ina Yun, Kyung Ran Park, and Yun-Han Lee. "Electro-hyperthermia up-regulates tumour suppressor Septin 4 to induce apoptotic cell death in hepatocellular carcinoma." International Journal of Hyperthermia 32, no. 6 (June 7, 2016): 648–56. http://dx.doi.org/10.1080/02656736.2016.1186290.

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Muñoz-Soriano, Verónica, and Nuria Paricio. "Overexpression of Septin 4, the Drosophila homologue of human CDCrel-1, is toxic for dopaminergic neurons." European Journal of Neuroscience 26, no. 11 (November 16, 2007): 3150–58. http://dx.doi.org/10.1111/j.1460-9568.2007.05937.x.

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Shehadeh, Lina, Georgia Mitsi, Nikhil Adi, Nanette Bishopric, and Spyridon Papapetropoulos. "Expression of Lewy body protein septin 4 in postmortem brain of Parkinson's disease and control subjects." Movement Disorders 24, no. 2 (January 30, 2009): 204–10. http://dx.doi.org/10.1002/mds.22306.

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Sitz, J. H., K. Baumgärtel, B. Hämmerle, C. Papadopoulos, P. Hekerman, F. J. Tejedor, W. Becker, and B. Lutz. "The down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4." Neuroscience 157, no. 3 (December 2008): 596–605. http://dx.doi.org/10.1016/j.neuroscience.2008.09.034.

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Rasmussen, Carolyn G., and N. Louise Glass. "A Rho-Type GTPase, rho-4, Is Required for Septation in Neurospora crassa." Eukaryotic Cell 4, no. 11 (November 2005): 1913–25. http://dx.doi.org/10.1128/ec.4.11.1913-1925.2005.

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ABSTRACT Proteins in the Rho family are small monomeric GTPases primarily involved in polarization, control of cell division, and reorganization of cytoskeletal elements. Phylogenetic analysis of predicted fungal Rho proteins suggests that a new Rho-type GTPase family, whose founding member is Rho4 from the archiascomycete Schizosaccharomyces pombe, is involved in septation. S. pombe rho4Δ mutants have multiple, abnormal septa. In contrast to S. pombe rho4Δ mutants, we show that strains containing rho-4 loss-of-function mutations in the filamentous fungus Neurospora crassa lead to a loss of septation. Epitope-tagged RHO-4 localized to septa and to the plasma membrane. In other fungi, the steps required for septation include formin, septin, and actin localization followed by cell wall synthesis and the completion of septation. rho-4 mutants were unable to form actin rings, showing that RHO-4 is required for actin ring formation. Characterization of strains containing activated alleles of rho-4 showed that RHO-4-GTP is likely to initiate new septum formation in N. crassa.

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Tóth, Kinga, Sándor Spisák, Orsolya Galamb, Ferenc Sipos, Barnabas Wichmann, Katalin Leiszter, Gabor Valcz, Zsolt Tulassay, and Béla Molnár. "S1981 Septin 9 mRNA, Protein Expression and Methylated DNA Level in Colorectal Adenoma-Dysplasia-Carcinoma Sequence." Gastroenterology 136, no. 5 (May 2009): A—306. http://dx.doi.org/10.1016/s0016-5085(09)61397-4.

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Randriamboavonjy, Voahanginirina, Johann Isaak, Amro Elgheznawy, Frank Pistrosch, Timo Frömel, Xiaoke Yin, Klaus Badenhoop, Heinrich Heide, Manuel Mayr, and Ingrid Fleming. "Calpain inhibition stabilizes the platelet proteome and reactivity in diabetes." Blood 120, no. 2 (July 12, 2012): 415–23. http://dx.doi.org/10.1182/blood-2011-12-399980.

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Abstract Platelets from patients with diabetes are hyperreactive and demonstrate increased adhesiveness, aggregation, degranulation, and thrombus formation, processes that contribute to the accelerated development of vascular disease. Part of the problem seems to be dysregulated platelet Ca2+ signaling and the activation of calpains, which are Ca2+-activated proteases that result in the limited proteolysis of substrate proteins and subsequent alterations in signaling. In the present study, we report that the activation of μ- and m-calpain in patients with type 2 diabetes has profound effects on the platelet proteome and have identified septin-5 and the integrin-linked kinase (ILK) as novel calpain substrates. The calpain-dependent cleavage of septin-5 disturbed its association with syntaxin-4 and promoted the secretion of α-granule contents, including TGF-β and CCL5. Calpain was also released by platelets and cleaved CCL5 to generate a variant with enhanced activity. Calpain activation also disrupted the ILK-PINCH-Parvin complex and altered platelet adhesion and spreading. In diabetic mice, calpain inhibition reversed the effects of diabetes on platelet protein cleavage, decreased circulating CCL5 levels, reduced platelet-leukocyte aggregate formation, and improved platelet function. The results of the present study indicate that diabetes-induced platelet dysfunction is mediated largely by calpain activation and suggest that calpain inhibition may be an effective way of preserving platelet function and eventually decelerating atherothrombosis development.

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Ma, Zhiyao, Dominic, Chi-chung Foo, Cherry S. Chan, KS Lau, and Wai Keung Leung. "Mo1072 EARLY MONITORING OF PLASMA METHYLATED SEPTIN 9 BY DROPLET DIGITAL POLYMERASE CHAIN REACTION IN PATIENTS WITH COLORECTAL CANCER." Gastroenterology 158, no. 6 (May 2020): S—779. http://dx.doi.org/10.1016/s0016-5085(20)32618-4.

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Lin, Cheng-Wen, Ping-Feng Tu, Nai-Wan Hsiao, Ching-Yao Chang, Lei Wan, Yu-Tsun Lin, and Hsueh-Wei Chang. "Identification of a novel septin 4 protein binding to human herpesvirus 8 kaposin A protein using a phage display cDNA library." Journal of Virological Methods 143, no. 1 (July 2007): 65–72. http://dx.doi.org/10.1016/j.jviromet.2007.02.010.

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Marcus, Jenna, Michal Bejerano-Sagie, Nicole Patterson, Susmita Bagchi, Vladislav V. Verkhusha, Diana Connolly, Gary L. Goldberg, et al. "Correction: Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions." Oncogene 39, no. 8 (October 1, 2019): 1830. http://dx.doi.org/10.1038/s41388-019-1039-4.

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Lewellyn, Lindsay, Ana Carvalho, Arshad Desai, Amy S. Maddox, and Karen Oegema. "The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly." Journal of Cell Biology 193, no. 1 (April 4, 2011): 155–69. http://dx.doi.org/10.1083/jcb.201008138.

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The chromosomal passenger complex (CPC) and centralspindlin are conserved cytokinesis regulators that localize to the spindle midzone, which forms between the separating chromosomes. Previous work placed the CPC and centralspindlin in a linear pathway that governs midzone formation. Using Caenorhabditis elegans embryos, we test whether there is a similar linear relationship between centralspindlin and the CPC in contractile ring constriction during cytokinesis. We show that simultaneous inhibition of the CPC kinase Aurora BAIR-2 and the centralspindlin component MKLP1ZEN-4 causes an additive constriction defect. Consistent with distinct roles for the proteins, inhibition of filamentous septin guanosine triphosphatases alleviates constriction defects in Aurora BAIR-2–inhibited embryos, whereas inhibition of Rac does so in MKLP1ZEN-4-inhibited embryos. Centralspindlin and the CPC are not required to enrich ring proteins at the cell equator but instead regulate formation of a compact mature ring. Therefore, in contrast to the linear midzone assembly pathway, centralspindlin and the CPC make independent contributions to control transformation of the sheet-like equatorial band into a ribbon-like contractile ring at the furrow tip.

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Garcia, Wanius, Ana Paula Ulian de Araújo, Flávio Lara, Debora Foguel, Manami Tanaka, Tomoo Tanaka, and Richard Charles Garratt. "An Intermediate Structure in the Thermal Unfolding of the GTPase Domain of Human Septin 4 (SEPT4/Bradeion-β) Forms Amyloid-like Filaments in Vitro†." Biochemistry 46, no. 39 (October 2007): 11101–9. http://dx.doi.org/10.1021/bi700702w.

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Muñoz-Soriano, Verónica, Rocío Nieto-Arellano, and Nuria Paricio. "Septin 4, the Drosophila Ortholog of Human CDCrel-1, Accumulates in parkin Mutant Brains and is Functionally Related to the Nedd4 E3 Ubiquitin Ligase." Journal of Molecular Neuroscience 48, no. 1 (May 6, 2012): 136–43. http://dx.doi.org/10.1007/s12031-012-9788-3.

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Leon Arellano, M., M. García-Arranz, R. Ruiz, R. Olivera, S. Magallares, S. Olmedillas-Lopez, T. Valdes-Sanchez, H. Guadalajara, and D. García-Olmo. "A First Step to a Biomarker of Curative Surgery in Colorectal Cancer by Liquid Biopsy of Methylated Septin 9 Gene." Disease Markers 2020 (June 5, 2020): 1–5. http://dx.doi.org/10.1155/2020/9761406.

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Objectives. To confirm that patients affected by colorectal cancer have the V2 region of Septin 9 (SEPT9) gene hypermethylated in the circulating free DNA from a peripheral blood sample before surgery and to determine if this hypermethylated DNA disappears from the patients after complete resection of the tumour. Methods. Plasma from 10 patients with colorectal cancer was collected preoperative and three months after surgery. The analysis of the methylation status of the promoter region of the SEPT9 gene was performed using a 7500 Fast Real-Time PCR System. Results. Hypermethylation of SEPT9 gene was detected in 8 out of 10 preoperative samples (one negative result was probed to be a Lynch syndrome) and in 4 out of 10 postoperative samples matching with the cases of recurrence or persistence of disease. This means that, in this sample, the preoperative sensitivity and specificity of the test were 88.9% and 100%, respectively, and there is 100% correlation between the positive results of the SEPT9 test and a recurrence/persistence of the disease in patients after surgical resection. Conclusions. Our study shows that circulating hypermethylated SEPT9 is a specific colorectal cancer biomarker. This hypermethylated SEPT9 DNA disappears around three months after surgery and that circulating hypermethylated SEPT9 may be the first noninvasive marker for postsurgical diagnosis; this conclusion must be confirmed with a more significant number of patients.

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Howe, Alicia G., Gregory D. Fairn, Kendra MacDonald, Vytas A. Bankaitis, and Christopher R. McMaster. "Regulation of Phosphoinositide Levels by the Phospholipid Transfer Protein Sec14p Controls Cdc42p/p21-Activated Kinase-Mediated Cell Cycle Progression at Cytokinesis." Eukaryotic Cell 6, no. 10 (June 29, 2007): 1814–23. http://dx.doi.org/10.1128/ec.00087-07.

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ABSTRACT Sec14p is an essential phosphatidylcholine/phosphatidylinositol transfer protein with a well-described role in the regulation of Golgi apparatus-derived vesicular transport in yeast. Inactivation of the CDP-choline pathway for phosphatidylcholine synthesis allows cells to survive in the absence of Sec14p function through restoration of Golgi vesicular transport capability. In this study, Saccharomyces cerevisiae cells containing a SEC14 temperature-sensitive allele along with an inactivated CDP-choline pathway were transformed with a high-copy-number yeast genomic library. Genes whose increased expression inhibited cell growth in the absence of Sec14p function were identified. Increasing levels of the Rho GTPase Cdc42p and its direct effector kinases Cla4p and Ste20p prevented the growth of cells lacking Sec14p and CDP-choline pathway function. Growth suppression was accompanied by an increase in large and multiply budded cells. This effect on polarized cell growth did not appear to be due to an inability to establish cell polarity, since both the actin cytoskeleton and localization of the septin Cdc12p were unaffected by increased expression of Cdc42p, Cla4p, or Ste20p. Nuclei were present in both the mother cell and the emerging bud, consistent with Sec14p regulation of the cell cycle subsequent to anaphase but prior to cytokinesis/septum breakdown. Increased expression of phosphatidylinositol 4-kinases and phosphatidylinositol 4-phosphate 5-kinase prevented growth arrest by CDC42, CLA4, or STE20 upon inactivation of Sec14p function. Sec14p regulation of phosphoinositide levels affects cytokinesis at the level of the Cdc42p/Cla4p/Ste20p signaling cascade.

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Potter, Nicholas T., Patrick Hurban, Mary N. White, Kara D. Whitlock, Catherine E. Lofton-Day, Reimo Tetzner, Thomas Koenig, Neil B. Quigley, and Gunter Weiss. "Validation of a Real-Time PCR–Based Qualitative Assay for the Detection of Methylated SEPT9 DNA in Human Plasma." Clinical Chemistry 60, no. 9 (September 1, 2014): 1183–91. http://dx.doi.org/10.1373/clinchem.2013.221044.

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Abstract BACKGROUND Epi proColon® is a new blood-based colorectal cancer (CRC) screening test designed to determine the methylation status of a promoter region of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe the analytical and clinical performance of the test. METHODS Analytical performance at 4 testing laboratories included determination of limit of detection, precision, and reproducibility of the SEPT9 test. Clinical performance was evaluated in a prospective study by use of samples (n = 1544) from subjects enrolled in the PRESEPT clinical trial. Results were analyzed by comparison with colonoscopy, the reference standard. RESULTS The limit of detection for methylated SEPT9 DNA was 7.8 pg/mL (95% CI 6–11 pg/mL) corresponding to <2 genome copies of methylated SEPT9 per milliliter of plasma. In the prospective clinical trial, sensitivity for all stages of CRC was 68% (95% CI 53%–80%) and for stage I–III CRC, 64% (48%–77%). Adjusted specificity, on the basis of negative colonoscopy findings, was 80.0% (78%–82%). SIGNIFICANCE: The Epi proColon test is a simple, real-time PCR–based assay for the detection of methylated SEPT9 DNA in blood that may provide a noninvasive CRC screening alternative for people noncompliant with current CRC screening guidelines.

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Clark, Kendra L., Omonseigho O. Talton, Shanthi Ganesan, Laura C. Schulz, and Aileen F. Keating. "Developmental origins of ovarian disorder: impact of maternal lean gestational diabetes on the offspring ovarian proteome in mice†." Biology of Reproduction 101, no. 4 (July 10, 2019): 771–81. http://dx.doi.org/10.1093/biolre/ioz116.

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Abstract Gestational diabetes mellitus (GDM) is an obstetric disorder affecting approximately 10% of pregnancies. The four high-fat, high-sucrose (HFHS) mouse model emulates GDM in lean women. Dams are fed a HFHS diet 1 week prior to mating and throughout gestation resulting in inadequate insulin response to glucose in mid-late pregnancy. The offspring of HFHS dams have increased adiposity, thus, we hypothesized that maternal metabolic alterations during lean GDM would compromise ovarian function in offspring both basally and in response to a control or HFHS diet in adulthood. Briefly, DLPL were lean dams and control diet pups; DLPH were lean dams and HFHS pups; DHPL were HFHS dams and control diet pups; and DHPH were HFHS dams and HFHS pups. A HFHS challenge in the absence of maternal GDM (DLPL vs. DLPH) increased 3 and decreased 30 ovarian proteins. Maternal GDM in the absence of a dietary stress (DLPL vs. DHPL) increased abundance of 4 proteins and decreased abundance of 85 proteins in the offspring ovary. Finally, 87 proteins increased, and 4 proteins decreased in offspring ovaries due to dietary challenge and exposure to maternal GDM in utero (DLPL vs. DHPH). Canopy FGF signaling regulator 2, deleted in azoospermia-associated protein 1, septin 7, and serine/arginine-rich splicing factor 2 were altered across multiple offspring groups. Together, these findings suggest a possible impact on fertility and oocyte quality in relation to GDM exposure in utero as well as in response to a western diet in later life.

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Zhang, Xiaoning, Wenwen Zhou, Peng Zhang, Fengxin Gao, Xiuling Zhao, Winnie Waichi Shum, and Xuhui Zeng. "Cabs1 Maintains Structural Integrity of Mouse Sperm Flagella during Epididymal Transit of Sperm." International Journal of Molecular Sciences 22, no. 2 (January 11, 2021): 652. http://dx.doi.org/10.3390/ijms22020652.

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The calcium-binding protein spermatid-associated 1 (Cabs1) is a novel spermatid-specific protein. However, its function remains largely unknown. In this study, we found that a long noncoding RNA (lncRNA) transcripted from the Cabs1 gene antisense, AntiCabs1, was also exclusively expressed in spermatids. Cabs1 and AntiCabs1 knockout mice were generated separately (using Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas9 methods) to investigate their functions in spermatogenesis. The genetic loss of Cabs1 did not affect testicular and epididymal development; however, male mice exhibited significantly impaired sperm tail structure and subfertility. Ultrastructural analysis revealed defects in sperm flagellar differentiation leading to an abnormal annulus and disorganization of the midpiece–principal piece junction, which may explain the high proportion of sperm with a bent tail. Interestingly, the proportion of sperm with a bent tail increased during transit in the epididymis. Furthermore, Western blot and immunofluorescence analyses showed that a genetic loss of Cabs1 decreased Septin 4 and Krt1 and increased cyclin Y-like 1 (Ccnyl1) levels compared with the wild type, suggesting that Cabs1 deficiency disturbed the expression of cytoskeleton-related proteins. By contrast, AntiCabs1−/− mice were indistinguishable from the wild type regarding testicular and epididymal development, sperm morphology, concentration and motility, and male fertility. This study demonstrates that Cabs1 is an important component of the sperm annulus essential for proper sperm tail assembly and motility.

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Zhang, Xiaoning, Wenwen Zhou, Peng Zhang, Fengxin Gao, Xiuling Zhao, Winnie Waichi Shum, and Xuhui Zeng. "Cabs1 Maintains Structural Integrity of Mouse Sperm Flagella during Epididymal Transit of Sperm." International Journal of Molecular Sciences 22, no. 2 (January 11, 2021): 652. http://dx.doi.org/10.3390/ijms22020652.

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The calcium-binding protein spermatid-associated 1 (Cabs1) is a novel spermatid-specific protein. However, its function remains largely unknown. In this study, we found that a long noncoding RNA (lncRNA) transcripted from the Cabs1 gene antisense, AntiCabs1, was also exclusively expressed in spermatids. Cabs1 and AntiCabs1 knockout mice were generated separately (using Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas9 methods) to investigate their functions in spermatogenesis. The genetic loss of Cabs1 did not affect testicular and epididymal development; however, male mice exhibited significantly impaired sperm tail structure and subfertility. Ultrastructural analysis revealed defects in sperm flagellar differentiation leading to an abnormal annulus and disorganization of the midpiece–principal piece junction, which may explain the high proportion of sperm with a bent tail. Interestingly, the proportion of sperm with a bent tail increased during transit in the epididymis. Furthermore, Western blot and immunofluorescence analyses showed that a genetic loss of Cabs1 decreased Septin 4 and Krt1 and increased cyclin Y-like 1 (Ccnyl1) levels compared with the wild type, suggesting that Cabs1 deficiency disturbed the expression of cytoskeleton-related proteins. By contrast, AntiCabs1−/− mice were indistinguishable from the wild type regarding testicular and epididymal development, sperm morphology, concentration and motility, and male fertility. This study demonstrates that Cabs1 is an important component of the sperm annulus essential for proper sperm tail assembly and motility.

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Bartsch, Ingrid, Ina Hainmann, Susanne Bläser, Anna Pavlova, Johannes Oldenburg, Anja Busse, Francois Lanza, Paquita Nurden, Andrea Superti-Furga, and Barbara Zieger. "Deletion of Two Contiguous Genes, Platelet GPIbβ (Glycoprotein Ibβ) and Septin SEPT5, in a Boy with Bernard-Soulier Syndrome and Developmental Delay: A Possible New Contiguous Gene Syndrome." Blood 108, no. 11 (November 16, 2006): 1097. http://dx.doi.org/10.1182/blood.v108.11.1097.1097.

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Abstract Mutations or deletions in the genes for platelet GPIb/V/IX (consisting of GPIbα, GPIbβ, GPV, GPIX) cause the bleeding disorder Bernard-Soulier syndrome. Septins are GTP-binding proteins essential for active membrane movement such as vesicle trafficking. In non-dividing cells (i.e. platelets) septins are implicated in exocytosis. Platelets from a SEPT5 knockout mouse show altered serotonin secretion and platelet aggregation suggesting that SEPT5 is involved in secretion in platelets. We report on a 4 year old boy born to consanguineous parents who developed several life-threatening mucosal bleeding episodes (when he suffered from upper respiratory infections) and showed developmental delay. Giant platelets were present in the blood smear, and ristocetin-induced platelet aggregation was reduced indicating that the boy suffered from Bernard-Soulier syndrome. Immune transmission electron microscopy of the platelets showed reduced expression of GPIb. PCR- and Southern analysis demonstrated that exon 1 and partly exon 2 of GPIbβ was deleted on both alleles. Further experiments showed that the deletion extended 5′ from exon 1 of GPIbβ to include the whole gene coding for SEPT5 located 5′ of GPIbβ. After bone marrow transplantation from a HLA-identical unrelated donor the boy developed no further bleeding symptoms. Conclusions: We identified a patient with Bernard-Soulier syndrome and mental retardation who had not only a homozygous deletion of exon 1 and partly exon 2 of GPIbβ but also a deletion of the whole adjacent SEPT5 gene, possibly indicating a novel contiguous gene syndrome. Whether absence of SEPT5 contributed to particularly severe bleeding symptoms and to developmental delay remains to be proven.

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Lazarevich, N. L., P. M. Abramov, M. D. Fedorova, I. F. Kustova, D. A. Shavochkina, A. N. Katargin, N. P. Kisseljova, et al. "Identification of a new methylation site in the Sept9 promoter region for the diagnosis of hepatocellular carcinoma." Advances in molecular oncology 6, no. 4 (December 15, 2019): 26–37. http://dx.doi.org/10.17650/2313-805x-2019-6-4-26-37.

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Background. Over 600,000 people die from hepatocellular carcinoma (HCC) each year worldwide. The disease is often detected at advanced stages and in many cases is not curable. Early diagnostic and monitoring of HCC recurrences remains a substantial problem in clinical oncology. That determines the need for a search for highly sensitive and specific biomarkers for the non-invasive of HCC diagnostics. The objective of the study. Identification of the hypermethylated locus in the promoter region of the septin 9 (Sept9) gene based on the annotated methylomes from the public databases. Experimental validation of methylation on a pilot panel of paired clinical samples of patients with HCC, as well as tissue samples from patients with benign liver tumors and lymphocytes from healthy donors. Materials and methods. To analyze the methyl data, samples of HCC from TCGA, hepatocellular adenoma from GEO (Gene Expression Omnibus) depository, peripheral blood cells and tissues of healthy donors from Methbank were used. Experimental validation of methylation levels of the identified site was carried out on a pilot panel of clinical samples by bisulphite pyrosequencing using PyroMark Q24.Results. Based on the analysis of methylome data, we selected cg20275528 site, which is characterized by high level of methylation in HCC tissues and minimal levels of methylation in non-tumor liver tissue, hepatocellular adenoma and peripheral blood of healthy donors. Experimental testing on a pilot panel of clinical specimens showed that the level of marker site methylation in HCC (42 % median) is significantly higher than in non-tumor liver tissues (3 % median) and benign neoplasms (1.5 % median) and exceeds the threshold value in HCC compared to paired samples of adjacent non-tumor liver tissue in 20 out of 30 studied cases (66.6 %). The general possibility for cg20275528 methylation detection in circulating DNA of plasma in HCC patients was shown.Conclusion. The obtained results indicate that the approach to the detection and experimental verification of diagnostically significant markers developed and tested in this study can be used to identify new differentially methylated sites and to establish new approaches for non-invasive HCC diagnosis.

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Takiguchi, Kingo, Yohko Tanaka-Takiguchi, and Makoto Kinoshita. "1SP6-04 Septin-induced robust membrane tubulation(1SP6 Membrane transformers!! : The combine and the dissociation to change the shape of biomembrane,The 47th Annual Meeting of the Biophysical Society of Japan)." Seibutsu Butsuri 49, supplement (2009): S8. http://dx.doi.org/10.2142/biophys.49.s8_3.

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Ardawi, M. Salleh M. "Effect of glutamine-enriched total parenteral nutrition on septic rats." Clinical Science 81, no. 2 (August 1, 1991): 215–22. http://dx.doi.org/10.1042/cs0810215.

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1. The effect of total parenteral nutrition with or without glutamine enrichment was studied in septic rats after 4 days of treatment. 2. Septic rats treated with glutamine-enriched total parenteral nutrition survived sepsis significantly better than other TPN-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with glutamine-enriched total parenteral nutrition was 25% compared with 55% in septic rats given total parenteral nutrition without glutamine and 70% in septic rats given glucose. 3. Glutamine-enriched total parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was the least negative as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P < 0.001) in response to glutamine-enriched total parenteral nutrition in septic rats. 5. The rate of protein synthesis was increased (21.2%) and the rate of protein degradation was decreased (35.5%) in response to glutamine-enriched total parenteral nutrition in septic rats. 6. It is concluded that the administration of glutamine-enriched total parenteral nutrition is beneficial to septic rats and possibly to septic patients.

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Koide, Masashi, Yuichi Tojo, Yoshihiro Hagiwara, Souichi Nakajima, Minoru Tanaka, Masahito Honda, and Eiji Itoi. "Arthroscopic Treatment of Septic Arthritis of the Elbow in a 4-Year-Old Girl." Case Reports in Orthopedics 2015 (2015): 1–4. http://dx.doi.org/10.1155/2015/853974.

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Pediatric septic arthritis is uncommon and has been traditionally treated by joint aspiration or open arthrotomy. There are some reports about arthroscopic surgery in pediatric septic arthritis of the knee, hip, and shoulder. However, there is no report for the case of elbow. We report a case of pediatric septic arthritis of elbow treated with arthroscopically with good clinical condition at 3-year follow-up. This paper is based on a report first published in Japanese (Tojo (2012)).

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Runtunuwu, Ari L., Jeanette I. Ch Manoppo, Dasril Daud, Irawan Yusuf, and Idham Jaya Ganda. "Prognostic value of nitric oxide in pediatric septic shock." Paediatrica Indonesiana 56, no. 4 (August 31, 2016): 211. http://dx.doi.org/10.14238/pi56.4.2016.211-4.

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Background Nitric oxide (NO) play a key role in the pathogenesis of septic shock. Nitrit oxide metabolite is reported as a good predictor for shock although its role as mortality predictor in sepsis still controversial.Objective To assess the serum nitric oxide (NO) levels and outcomes in pediatric patients with septic shock.Methods We conducted a prospective cohort study from January 2013 to April 2014 in Pediatric Intensive Care Unit (PICU) Prof. Dr. R. D. Kandou Hospital, Manado. Subjects were patients aged 1 month-12 years diagnosed with septic shock. We measured initial serum NO and observed its outcomes in all subjects.Results A total of 37 patients with septic shock met the study criteria. Nineteen children were male (51.4%). Seventeen subjects died and 20 subjects survived. The mean age of subjects with septic shock was 37.3 (SD 14.2) months. The mean serum NO level was significantly higher in the group who died [33.2 μM; 95% CI 23.6 to 42.7] than in the group who survived [13.8 μM; 95%CI 11.6 to 15.9] (P<0.01). The serum NO cut-off point for predicting mortality was 16.15 µM. For NO levels of more than 16.15 µM, the positive predictive value was 72.2% and negative predictive value was 78.9% (OR 9.750; 95%CI 2.154 to 44.138).Conclusion In pediatric patients with septic shock, serum NO levels are significantly higher in those who died than in those who survived. Serum nitric oxide level can be used to predict outcomes of patients with septic shock.

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Weiss, Scott L., and Clifford S. Deutschman. "Are septic children really just “septic little adults”?" Intensive Care Medicine 44, no. 3 (January 22, 2018): 392–94. http://dx.doi.org/10.1007/s00134-017-5041-4.

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Salleh, M., and M. Ardawi. "Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic rats." Clinical Science 82, no. 4 (April 1, 1992): 419–27. http://dx.doi.org/10.1042/cs0820419.

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1. The effects of parenteral nutrition with or without xylitol and/or glutamine supplementation were studied in septic rats after 4 days of treatment. 2. Septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition survived sepsis significantly better than other parenteral nutrition-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with xylitol-glutamine-supplemented parenteral nutrition was 9.5% compared with 54.5% in septic rats given parenteral nutrition without xylitol and glutamine, and 52.4% in septic rats treated with parenteral nutrition supplemented with glucose. 3. Xylitol- and/or glutamine-supplemented parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was positive in the rats given xylitol-supplemented parenteral nutrition and more positive when rats were treated with xylitol-glutamine-supplemented parenteral nutrition, as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P < 0.001) in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 5. Hepatic protein and RNA contents were increased in septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. Similarly, protein and RNA contents were markedly increased in muscles of septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. 6. The rates of incorporation of leucine/tyrosine into liver/muscle proteins in vitro were increased and the rate of muscular tyrosine release was decreased in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 7. It is concluded that the administration of xylitol- and/ or glutamine-supplemented parenteral nutrition is beneficial to septic rats and possibly to septic patients.

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Ahmed, Rabab Mahmoud, Amin R. Soliman, Ahmad Yousry, Khaled Marzouk, and Farouk Faris. "Efficacy of 4-hour rescue therapeutic plasma exchange in severe septic shock patients." Romanian Journal of Internal Medicine 58, no. 2 (June 1, 2020): 75–80. http://dx.doi.org/10.2478/rjim-2019-0026.

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AbstractBackground.Early intervention for septic shock is crucial to reduce mortality and improve outcome. There is still a great debate over the exact time of therapeutic plasma exchange (TPE) administration in septic shock patients. This study aims to investigate the effect of early initiation (within 4 hours) of TPE in severe septic shock on hemodynamics & outcome.Methods. We conducted a prospective, before-after case series study on 16 septic shock patients requiring high doses of vasopressors admitted in two ICUs from Cairo, Egypt. All of our patients received TPE within 4 hours of ICU admission. The fresh frozen plasma exchange volume = 1.5 × plasma volume.Results. In the 16 patients included in the study, mean arterial pressure was significantly improved after the initial TPE (p < 0.002) and norepinephrine dose which significantly reduced post TPE (p < 0.001). In addition, norepinephrine dose to mean arterial pressure significantly improved (p < 0.001). There was reduction of a net 6 hours fluid balances following the first TPE were observed in all the patients (p < 0.03) by a mean of 757 ml. Systemic vascular resistance index was markedly improved post-TPE along with statistically improved cardiac index (p < 0.01). Stroke volume variance was also significantly decreased after the TPE sessions (p < 0.01). C-reactive protein significantly improved after TPE (P < 0.01).Conclusion. Early initiation of TPE in severe septic shock patients might improve hemodynamic measures.

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Lee, Wonhwa, O. Yuseok, Sumin Yang, Bong‐Seon Lee, Jee‐Hyun Lee, Eui Kyun Park, Moon‐Chang Baek, Gyu‐Yong Song, and Jong‐Sup Bae. "JH‐4 reduces HMGB1‐mediated septic responses and improves survival rate in septic mice." Journal of Cellular Biochemistry 120, no. 4 (October 30, 2018): 6277–89. http://dx.doi.org/10.1002/jcb.27914.

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Malik, Pushpendra, Sanjeev Singla, M. K. Garg, and Rohit Virmani. "Septic abortion leading to intestinal perforation- 4 case reports with Review of literature." Asian Pacific Journal of Health Sciences 5, no. 3 (July 2018): 300–301. http://dx.doi.org/10.21276/apjhs.2018.5.3.43.

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Journal articles on the topic 'Septin 4'

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