Relevant bibliographies by topics / RhoGDIα / Journal articles
To see the other types of publications on this topic, follow the link: RhoGDIα.

Journal articles on the topic 'RhoGDIα'

Author: Grafiati
Published: 10 January 2023
Last updated: 28 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'RhoGDIα.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Michaelson, David, Joseph Silletti, Gretchen Murphy, Peter D'Eustachio, Mark Rush, and Mark R. Philips. "Differential Localization of Rho Gtpases in Live Cells." Journal of Cell Biology 152, no. 1 (January 8, 2001): 111–26. http://dx.doi.org/10.1083/jcb.152.1.111.

Full text
Abstract:
Determinants of membrane targeting of Rho proteins were investigated in live cells with green fluorescent fusion proteins expressed with or without Rho-guanine nucleotide dissociation inhibitor (GDI)α. The hypervariable region determined to which membrane compartment each protein was targeted. Targeting was regulated by binding to RhoGDIα in the case of RhoA, Rac1, Rac2, and Cdc42hs but not RhoB or TC10. Although RhoB localized to the plasma membrane (PM), Golgi, and motile peri-Golgi vesicles, TC10 localized to PMs and endosomes. Inhibition of palmitoylation mislocalized H-Ras, RhoB, and TC10 to the endoplasmic reticulum. Although overexpressed Cdc42hs and Rac2 were observed predominantly on endomembrane, Rac1 was predominantly at the PM. RhoA was cytosolic even when expressed at levels in vast excess of RhoGDIα. Oncogenic Dbl stimulated translocation of green fluorescent protein (GFP)-Rac1, GFP-Cdc42hs, and GFP-RhoA to lamellipodia. RhoGDI binding to GFP-Cdc42hs was not affected by substituting farnesylation for geranylgeranylation. A palmitoylation site inserted into RhoA blocked RhoGDIα binding. Mutations that render RhoA, Cdc42hs, or Rac1, either constitutively active or dominant negative abrogated binding to RhoGDIα and redirected expression to both PMs and internal membranes. Thus, despite the common essential feature of the CAAX (prenylation, AAX tripeptide proteolysis, and carboxyl methylation) motif, the subcellular localizations of Rho GTPases, like their functions, are diverse and dynamic.
APA, Harvard, Vancouver, ISO, and other styles
2

Giang Ho, T. T., Audrey Stultiens, Johanne Dubail, Charles M. Lapière, Betty V. Nusgens, Alain C. Colige, and Christophe F. Deroanne. "RhoGDIα-dependent balance between RhoA and RhoC is a key regulator of cancer cell tumorigenesis." Molecular Biology of the Cell 22, no. 17 (September 2011): 3263–75. http://dx.doi.org/10.1091/mbc.e11-01-0020.

Full text
Abstract:
RhoGTPases are key signaling molecules regulating main cellular functions such as migration, proliferation, survival, and gene expression through interactions with various effectors. Within the RhoA-related subclass, RhoA and RhoC contribute to several steps of tumor growth, and the regulation of their expression affects cancer progression. Our aim is to investigate their respective contributions to the acquisition of an invasive phenotype by using models of reduced or forced expression. The silencing of RhoC, but not of RhoA, increased the expression of genes encoding tumor suppressors, such as nonsteroidal anti-inflammatory drug–activated gene 1 (NAG-1), and decreased migration and the anchorage-independent growth in vitro. In vivo, RhoC small interfering RNA (siRhoC) impaired tumor growth. Of interest, the simultaneous knockdown of RhoC and NAG-1 repressed most of the siRhoC-related effects, demonstrating the central role of NAG-1. In addition of being induced by RhoC silencing, NAG-1 was also largely up-regulated in cells overexpressing RhoA. The silencing of RhoGDP dissociation inhibitor α (RhoGDIα) and the overexpression of a RhoA mutant unable to bind RhoGDIα suggested that the effect of RhoC silencing is indirect and results from the up-regulation of the RhoA level through competition for RhoGDIα. This study demonstrates the dynamic balance inside the RhoGTPase network and illustrates its biological relevance in cancer progression.
APA, Harvard, Vancouver, ISO, and other styles
3

El Marzouk, Saad, Jennifer R. Schultz-Norton, Varsha S. Likhite, Ian X. McLeod, John R. Yates, and Ann M. Nardulli. "Rho GDP dissociation inhibitor α interacts with estrogen receptor α and influences estrogen responsiveness." Journal of Molecular Endocrinology 39, no. 4 (October 2007): 249–59. http://dx.doi.org/10.1677/jme-07-0055.

Full text
Abstract:
AbstractEstrogen receptor α (ERα) is a ligand-activated transcription factor that regulates expression of estrogen-responsive genes. Upon binding of the ligand-occupied ERα to estrogen response elements (EREs) in DNA, the receptor interacts with a variety of coregulatory proteins to modulate transcription of target genes. We have isolated and identified a number of proteins associated with the DNA-bound ERα. One of these proteins, Rho guanosine diphosphate (GDP) dissociation inhibitor α (RhoGDIα), is a negative regulator of the Rho family of GTP-binding proteins. In this study, we demonstrate that endogenously expressed RhoGDIα is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, and that RhoGDIα binds directly to ERα, alters the ERα–ERE interaction, and influences the ability of ERα to regulate transcription of a heterologous estrogen-responsive reporter plasmid in transient transfection assays as well as endogenous, estrogen-responsive genes in MCF-7 cells. Our studies suggest that, in addition to the activity of RhoGDIα in the cytoplasm, it also influences ERα signaling in the nucleus.
APA, Harvard, Vancouver, ISO, and other styles
4

Dransart, E., A. Morin, J. Cherfils, and B. Olofsson. "RhoGDI-3, a promising system to investigate the regulatory function of rhoGDIs: uncoupling of inhibitory and shuttling functions of rhoGDIs." Biochemical Society Transactions 33, no. 4 (August 1, 2005): 623–26. http://dx.doi.org/10.1042/bst0330623.

Full text
Abstract:
rhoGDIs (Rho GDP dissociation inhibitors) are postulated to regulate the activity and the localization of small G-proteins of the Rho family by a shuttling process involving extraction of Rho from donor membranes, formation of inhibitory cytosolic rhoGDI/Rho complexes, and delivery of Rho to target membranes. However, the role of rhoGDIs in site-specific membrane targeting or extraction of Rho is still poorly understood. We investigated here the in vivo functions of two mammalian rhoGDIs: the specific rhoGDI-3 and the well-studied rhoGDI-1 (rhoGDI) after structure-based mutagenesis. We identified two sites in rhoGDIs, forming conserved interactions with their Rho target, whose mutation results in the uncoupling of inhibitory and shuttling functions of rhoGDIs in vivo. Remarkably, these rhoGDI mutants were detected at Rho-induced membrane ruffles or protrusions, where they co-localized with RhoG or Cdc42, probably identifying for the first time the site of extraction of a Rho protein by a rhoGDI in vivo. We propose that these mutations act by modifying the steady-state kinetics of the shuttling process regulated by rhoGDIs, such that transient steps at the cell membranes now become detectable. They should provide valuable tools for future investigations of the dynamics of membrane extraction or delivery of Rho proteins and their regulation by cellular partners.
APA, Harvard, Vancouver, ISO, and other styles
5

Zhu, Yezi, Ramakumar Tummala, Chengfei Liu, Nagalakshmi Nadiminty, Wei Lou, Christopher P. Evans, Qinghua Zhou, and Allen C. Gao. "RhoGDIα suppresses growth and survival of prostate cancer cells." Prostate 72, no. 4 (June 16, 2011): 392–98. http://dx.doi.org/10.1002/pros.21441.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Zhu, Yezi, Chengfei Liu, Ramakumar Tummala, Nagalakshmi Nadiminty, Wei Lou, and Allen C. Gao. "RhoGDIα downregulates androgen receptor signaling in prostate cancer cells." Prostate 73, no. 15 (August 6, 2013): 1614–22. http://dx.doi.org/10.1002/pros.22615.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Wu, Fan, Peishan Hu, Dengke Li, Yan Hu, Yingjiao Qi, Bin Yin, Tao Jiang, Jiangang Yuan, Wei Han, and Xiaozhong Peng. "RhoGDIα suppresses self-renewal and tumorigenesis of glioma stem cells." Oncotarget 7, no. 38 (August 19, 2016): 61619–29. http://dx.doi.org/10.18632/oncotarget.11423.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Auguste, David, Mirela Maier, Cindy Baldwin, Lamine Aoudjit, Richard Robins, Indra R. Gupta, and Tomoko Takano. "Disease-causing mutations of RhoGDIα induce Rac1 hyperactivation in podocytes." Small GTPases 7, no. 2 (January 4, 2016): 107–21. http://dx.doi.org/10.1080/21541248.2015.1113353.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Li, Xuemin, Yandong Zhao, Panhong Liu, Xiaoqing Zhu, Minyi Chen, Huadong Wang, Daxiang Lu, and Renbin Qi. "Senegenin Inhibits Hypoxia/Reoxygenation-Induced Neuronal Apoptosis by Upregulating RhoGDIα." Molecular Neurobiology 52, no. 3 (November 4, 2014): 1561–71. http://dx.doi.org/10.1007/s12035-014-8948-6.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Kuhlmann, Nora, Sarah Wroblowski, Lukas Scislowski, and Michael Lammers. "RhoGDIα Acetylation at K127 and K141 Affects Binding toward Nonprenylated RhoA." Biochemistry 55, no. 2 (January 4, 2016): 304–12. http://dx.doi.org/10.1021/acs.biochem.5b01242.

Full text
APA, Harvard, Vancouver, ISO, and other styles
11

Oishi, Atsuro, Noriko Makita, Junichiro Sato, and Taroh Iiri. "Regulation of RhoA Signaling by the cAMP-dependent Phosphorylation of RhoGDIα." Journal of Biological Chemistry 287, no. 46 (September 25, 2012): 38705–15. http://dx.doi.org/10.1074/jbc.m112.401547.

Full text
APA, Harvard, Vancouver, ISO, and other styles
12

Qi, Yan, Xiuying Liang, Haijing Guan, Jingwen Sun, and Wenjuan Yao. "RhoGDI1-Cdc42 Signaling Is Required for PDGF-BB-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Neointima Formation." Biomedicines 9, no. 9 (September 6, 2021): 1169. http://dx.doi.org/10.3390/biomedicines9091169.

Full text
Abstract:
RhoGTPase is involved in PDGF-BB-mediated VSMC phenotypic modulation. RhoGDIs are key factors in regulating RhoGTPase activation. In the present study, we investigated the regulatory effect of RhoGDI1 on the activation of RhoGTPase in VSMC transformation and neointima formation. Western blot and co-immunoprecipitation assays showed that the PDGF receptor inhibition by crenolanib promoted RhoGDI1 polyubiquitination and degradation. Inhibition of RhoGDI1 degradation via MG132 reversed the decrease in VSMC phenotypic transformation. In addition, RhoGDI1 knockdown significantly inhibited VSMC phenotypic transformation and neointima formation in vitro and in vivo. These results suggest that PDGF-BB promotes RhoGDI1 stability via the PDGF receptor and induces the VSMC synthetic phenotype. The co-immunoprecipitation assay showed that PDGF-BB enhanced the interaction of RhoGDI1 with Cdc42 and promoted the activation of Cdc42; these enhancements were blocked by crenolanib and RhoGDI1 knockdown. Moreover, RhoGDI1 knockdown and crenolanib pretreatment prevented the localization of Cdc42 to the plasma membrane (PM) to activate and improve the accumulation of Cdc42 on endoplasmic reticulum (ER). Furthermore, Cdc42 inhibition or suppression significantly reduced VSMC phenotypic transformation and neointima formation in vitro and in vivo. This study revealed the novel mechanism by which RhoGDI1 stability promotes the RhoGDI1-Cdc42 interaction and Cdc42 activation, thereby affecting VSMC phenotypic transformation and neointima formation.
APA, Harvard, Vancouver, ISO, and other styles
13

CUSTODIS, F., M. EBERL, H. KILTER, M. BOHM, and U. LAUFS. "Association of RhoGDIα with Rac1 GTPase mediates free radical production during myocardial hypertrophy." Cardiovascular Research 71, no. 2 (July 15, 2006): 342–51. http://dx.doi.org/10.1016/j.cardiores.2006.04.005.

Full text
APA, Harvard, Vancouver, ISO, and other styles
14

RONG, F., W. LI, K. CHEN, D. M. LI, W. M. DUAN, Y. Z. FENG, F. LI, et al. "Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel." Neoplasma 59, no. 05 (2012): 541–50. http://dx.doi.org/10.4149/neo_2012_070.

Full text
APA, Harvard, Vancouver, ISO, and other styles
15

Zhu, Junlan, Yang Li, Caiyi Chen, Jiugao Ma, Wenrui Sun, Zhongxian Tian, Jingxia Li, et al. "NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein." Neoplasia 19, no. 9 (September 2017): 672–83. http://dx.doi.org/10.1016/j.neo.2017.06.002.

Full text
APA, Harvard, Vancouver, ISO, and other styles
16

Kuhlmann, Nora, Sarah Wroblowski, Philipp Knyphausen, Susanne de Boor, Julian Brenig, Anke Y. Zienert, Katrin Meyer-Teschendorf, et al. "Structural and Mechanistic Insights into the Regulation of the Fundamental Rho Regulator RhoGDIα by Lysine Acetylation." Journal of Biological Chemistry 291, no. 11 (December 30, 2015): 5484–99. http://dx.doi.org/10.1074/jbc.m115.707091.

Full text
APA, Harvard, Vancouver, ISO, and other styles
17

Wang, Li, Jinsong Pan, Tingle Wang, Meng Song, and Wantao Chen. "Pathological Cyclic Strain-Induced Apoptosis in Human Periodontal Ligament Cells through the RhoGDIα/Caspase-3/PARP Pathway." PLoS ONE 8, no. 10 (October 10, 2013): e75973. http://dx.doi.org/10.1371/journal.pone.0075973.

Full text
APA, Harvard, Vancouver, ISO, and other styles
18

Li, Xinhua, and Alan Yiu Wah Lee. "Semaphorin 5A and Plexin-B3 Inhibit Human Glioma Cell Motility through RhoGDIα-mediated Inactivation of Rac1 GTPase." Journal of Biological Chemistry 285, no. 42 (August 9, 2010): 32436–45. http://dx.doi.org/10.1074/jbc.m110.120451.

Full text
APA, Harvard, Vancouver, ISO, and other styles
19

Xiao, Yang, Vivian Y. Lin, Shi Ke, Gregory E. Lin, Fang-Tsyr Lin, and Weei-Chin Lin. "Erratum for Xiao et al., 14-3-3τ Promotes Breast Cancer Invasion and Metastasis by Inhibiting RhoGDIα." Molecular and Cellular Biology 34, no. 16 (July 18, 2014): 3180. http://dx.doi.org/10.1128/mcb.00825-14.

Full text
APA, Harvard, Vancouver, ISO, and other styles
20

Hooshmand, Somayeh, Abbas Ghaderi, Khatijah Yusoff, Thilakavathy Karrupiah, Rozita Rosli, and Zahra Mojtahedi. "Downregulation of RhoGDIα increased migration and invasion of ER+MCF7 and ER−MDA-MB-231 breast cancer cells." Cell Adhesion & Migration 7, no. 3 (May 5, 2013): 297–303. http://dx.doi.org/10.4161/cam.24204.

Full text
APA, Harvard, Vancouver, ISO, and other styles
21

Lu, Yan, Xiujie Liu, Jianfeng Zhou, Aijun Huang, Jiazhen Zhou, and Cheng He. "TROY Interacts with Rho Guanine Nucleotide Dissociation Inhibitor α (RhoGDIα) to Mediate Nogo-induced Inhibition of Neurite Outgrowth." Journal of Biological Chemistry 288, no. 47 (October 15, 2013): 34276–86. http://dx.doi.org/10.1074/jbc.m113.519744.

Full text
APA, Harvard, Vancouver, ISO, and other styles
22

Ngo, Anh T. P., Marisa L. D. Thierheimer, Özgün Babur, Anne D. Rocheleau, Tao Huang, Jiaqing Pang, Rachel A. Rigg, et al. "Assessment of roles for the Rho-specific guanine nucleotide dissociation inhibitor Ly-GDI in platelet function: a spatial systems approach." American Journal of Physiology-Cell Physiology 312, no. 4 (April 1, 2017): C527—C536. http://dx.doi.org/10.1152/ajpcell.00274.2016.

Full text
Abstract:
On activation at sites of vascular injury, platelets undergo morphological alterations essential to hemostasis via cytoskeletal reorganizations driven by the Rho GTPases Rac1, Cdc42, and RhoA. Here we investigate roles for Rho-specific guanine nucleotide dissociation inhibitor proteins (RhoGDIs) in platelet function. We find that platelets express two RhoGDI family members, RhoGDI and Ly-GDI. Whereas RhoGDI localizes throughout platelets in a granule-like manner, Ly-GDI shows an asymmetric, polarized localization that largely overlaps with Rac1 and Cdc42 as well as microtubules and protein kinase C (PKC) in platelets adherent to fibrinogen. Antibody interference and platelet spreading experiments suggest a specific role for Ly-GDI in platelet function. Intracellular signaling studies based on interactome and pathways analyses also support a regulatory role for Ly-GDI, which is phosphorylated at PKC substrate motifs in a PKC-dependent manner in response to the platelet collagen receptor glycoprotein (GP) VI–specific agonist collagen-related peptide. Additionally, PKC inhibition diffuses the polarized organization of Ly-GDI in spread platelets relative to its colocalization with Rac1 and Cdc42. Together, our results suggest a role for Ly-GDI in the localized regulation of Rho GTPases in platelets and hypothesize a link between the PKC and Rho GTPase signaling systems in platelet function.
APA, Harvard, Vancouver, ISO, and other styles
23

Cao, Zipeng, Xueyong Li, Jingxia Li, Beipei Kang, Jingyuan Chen, Wenjing Luo, and Chuanshu Huang. "SUMOylation of RhoGDIα is required for its repression of cyclin D1 expression and anchorage-independent growth of cancer cells." Molecular Oncology 8, no. 2 (December 3, 2013): 285–96. http://dx.doi.org/10.1016/j.molonc.2013.11.006.

Full text
APA, Harvard, Vancouver, ISO, and other styles
24

Chen, Yi-Chyan, Fu-Ming Tsai, and Mao-Liang Chen. "Antipsychotic Drugs Reverse MK801-Inhibited Cell Migration and F-actin Condensation by Modulating the Rho Signaling Pathway in B35 Cells." Behavioural Neurology 2020 (November 10, 2020): 1–9. http://dx.doi.org/10.1155/2020/4163274.

Full text
Abstract:
Background and Aim. MK801-induced psychotic symptoms and also the Ras homolog family member A (RhoA) expression and cell division control protein 42 (cdc42) mRNA modulation in the rat brain have been investigated. Antipsychotic drugs (APDs) have been reported to induce Rho GDP-dissociation inhibitor (RhoGDI) pathway regulation related to cytoskeleton reorganization in neuronal cells. It will be necessary to clarify the effects of APDs on MK801-induced RhoGDI signaling regulation in neuronal cells. Methods. B35 neuronal cells were treated with MK801 for 7 days then treated with MK801 in combination with haloperidol or clozapine for a further 7 days. Cell migration, F-actin condensation, and RhoGDI signaling regulation were examined to investigate the regulatory effects of MK801, haloperidol, and clozapine in B35 neuronal cells. Results. MK801 reduced B35 cell migration, whereas both haloperidol and clozapine reversed the reduction in cell migration induced by MK801. Haloperidol and clozapine restored F-actin condensation after it was diminished by MK801 in B35 cell nuclei. MK801 increased the RhoGDI1 and RhoA expression, which was diminished by the addition of haloperidol and clozapine. MK801 reduced the CDC42 expression, which was restored by haloperidol and clozapine. MK801 reduced the Rho-associated coiled-coil containing protein kinase 1 (ROCK1), profilin1 (PFN1), and neuronal Wiskott–Aldrich Syndrome protein (N-WASP) expression, which was further reduced by haloperidol and clozapine. MK801 also increased the phosphorylated myosin light chain 2 (p-MLC2), postsynaptic density protein 95 (PSD-95), and c-jun expression, which was decreased by haloperidol and clozapine. p21 (RAC1-) activated kinase 1 (PAK1) expression was not affected by MK801.
APA, Harvard, Vancouver, ISO, and other styles
25

Dovas, Athanassios, Youngsil Choi, Atsuko Yoneda, Hinke A. B. Multhaupt, Seung-Hae Kwon, Dongmin Kang, Eok-Soo Oh, and John R. Couchman. "Serine 34 Phosphorylation of Rho Guanine Dissociation Inhibitor (RhoGDIα) Links Signaling from Conventional Protein Kinase C to RhoGTPase in Cell Adhesion." Journal of Biological Chemistry 285, no. 30 (May 15, 2010): 23296–308. http://dx.doi.org/10.1074/jbc.m109.098129.

Full text
APA, Harvard, Vancouver, ISO, and other styles
26

Logan, Michael R., Lynden Jones, Daniel Forsberg, Alex Bodman, Alicia Baier, and Gary Eitzen. "Functional analysis of RhoGDI inhibitory activity on vacuole membrane fusion." Biochemical Journal 434, no. 3 (February 24, 2011): 445–57. http://dx.doi.org/10.1042/bj20101759.

Full text
Abstract:
RhoGDIs (Rho GDP-dissociation inhibitors) are the natural inhibitors of Rho GTPases. They interfere with Rho protein function by either blocking upstream activation or association with downstream signalling molecules. RhoGDIs can also extract membrane-bound Rho GTPases to form soluble cytosolic complexes. We have shown previously that purified yeast RhoGDI Rdi1p, can inhibit vacuole membrane fusion in vitro. In the present paper we functionally dissect Rdi1p to discover its mode of regulating membrane fusion. Overexpression of Rdi1p in vivo profoundly affected cell morphology including increased actin patches in mother cells indicative of polarity defects, delayed ALP (alkaline phosphatase) sorting and the presence of highly fragmented vacuoles indicative of membrane fusion defects. These defects were not caused by the loss of typical transport and fusion proteins, but rather were linked to the reduction of membrane localization and activation of Cdc42p and Rho1p. Subcellular fractionation showed that Rdi1p is predominantly a cytosolic monomer, free of bound Rho GTPases. Overexpression of endogenous Rdi1p, or the addition of exogenous Rdi1p, generated stable cytosolic complexes. Rdi1p structure–function analysis showed that membrane association via the C-terminal β-sheet domain was required for the functional inhibition of membrane fusion. Furthermore, Rdi1p inhibited membrane fusion through the binding of Rho GTPases independent from its extraction activity.
APA, Harvard, Vancouver, ISO, and other styles
27

Zhu, Junlan, Yang Lii, Caiyi Chen, Jiugao Ma, Wenrui Sun, Zhongxian Tian, Jingxia Li, et al. "Corrigendum to “NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein” [Neoplasia 19 (2017) 672–683]." Neoplasia 23, no. 12 (December 2021): 1179–82. http://dx.doi.org/10.1016/j.neo.2021.09.007.

Full text
APA, Harvard, Vancouver, ISO, and other styles
28

Boulter, Etienne, and Rafael Garcia-Mata. "RhoGDI." Small GTPases 1, no. 1 (July 2010): 65–68. http://dx.doi.org/10.4161/sgtp.1.1.12990.

Full text
APA, Harvard, Vancouver, ISO, and other styles
29

Cho, Kim, Baek, Kim, and Lee. "Regulation of Rho GTPases by RhoGDIs in Human Cancers." Cells 8, no. 9 (September 5, 2019): 1037. http://dx.doi.org/10.3390/cells8091037.

Full text
Abstract:
Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.
APA, Harvard, Vancouver, ISO, and other styles
30

Scheible, Nolan, Gyeong Mee Yoon, and Andrew G. McCubbin. "Calmodulin Domain Protein Kinase PiCDPK1 Regulates Pollen Tube Growth Polarity through Interaction with RhoGDI." Plants 11, no. 3 (January 19, 2022): 254. http://dx.doi.org/10.3390/plants11030254.

Full text
Abstract:
The pollen-specific calcium-dependent protein kinase PiCDPK1 of Petunia inflata has previously been shown to regulate polarity in tip growth in pollen tubes. Here we report the identification of a Rho Guanine Dissociation Inhibitor (PiRhoGDI1) as a PiCDPK1 interacting protein. We demonstrate that PiRhoGDI1 and PiCDPK1 interact in a yeast 2-hybrid assay, as well as in an in vitro pull-down assay, and that PiRhoGDI1 is phosphorylated by PiCDPK1 in vitro. We further demonstrate the PiRhoGDI1 is capable of rescuing the loss of growth polarity phenotype caused by over-expressing PiCDPK1 in vivo using stable transgenic plants. We confirmed that PiRhoGDI1 interacts with a pollen-expressed ROP GTPase isoform consistent with the established role of RhoGDIs in negatively regulating GTPases through their membrane removal and locking them in an inactive cytosolic complex. ROP is a central regulator of polarity in tip growth, upstream of Ca2+, and PiCDPK1 over-expression has been previously reported to lead to dramatic elevation of cytosolic Ca2+ through a positive feedback loop. The discovery that PiCDPK1 impacts ROP regulation via PiRhoGDI1 suggests that PiCDPK1 acts as RhoGDI displacement factor and leads us to propose a model which we hypothesize regulates the rapid recycling of ROP GTPase at the pollen tube tip.
APA, Harvard, Vancouver, ISO, and other styles
31

Kim, Hyo-Jin, Ki-Jun Ryu, Minju Kim, Taeyoung Kim, Seon-Hee Kim, Hyeontak Han, Hyemin Kim, et al. "RhoGDI2-Mediated Rac1 Recruitment to Filamin A Enhances Rac1 Activity and Promotes Invasive Abilities of Gastric Cancer Cells." Cancers 14, no. 1 (January 5, 2022): 255. http://dx.doi.org/10.3390/cancers14010255.

Full text
Abstract:
Rho GDP dissociation inhibitor 2 (RhoGDI2), a regulator of Rho family GTPase, has been known to promote tumor growth and malignant progression in gastric cancer. We previously showed that RhoGDI2 positively regulates Rac1 activity and Rac1 activation is critical for RhoGDI2-induced gastric cancer cell invasion. In this study, to identify the precise molecular mechanism by which RhoGDI2 activates Rac1 activity, we performed two-hybrid screenings using yeast and found that RhoGDI2 plays an important role in the interaction between Rac1, Filamin A and Rac1 activation in gastric cancer cells. Moreover, we found that Filamin A is required for Rac1 activation and the invasive ability of gastric cancer cells. Depletion of Filamin A expression markedly reduced Rac1 activity in RhoGDI2-expressing gastric cancer cells. The migration and invasion ability of RhoGDI2-expressing gastric cancer cells also substantially decreased when Filamin A expression was depleted. Furthermore, we found that Trio, a Rac1-specific guanine nucleotide exchange factor (GEF), is critical for Rac1 activation and the invasive ability of gastric cancer cells. Therefore, we conclude that RhoGDI2 increases Rac1 activity by recruiting Rac1 to Filamin A and enhancing the interaction between Rac1 and Trio, which is critical for the invasive ability of gastric cancer cells.
APA, Harvard, Vancouver, ISO, and other styles
32

Elfenbein, Arye, John M. Rhodes, Julia Meller, Martin A. Schwartz, Michiyuki Matsuda, and Michael Simons. "Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway." Journal of Cell Biology 186, no. 1 (July 6, 2009): 75–83. http://dx.doi.org/10.1083/jcb.200810179.

Full text
Abstract:
Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive state by RhoGDI1, which is found in a ternary complex with synectin and S4. Binding of S4 to synectin increases the latter's binding to RhoGDI1, which in turn enhances RhoGDI1's affinity for RhoG. S4 clustering activates PKCα, which phosphorylates RhoGDI1 at Ser96. This phosphorylation triggers release of RhoG, leading to polarized activation of Rac1. Thus, FGF2-induced Rac1 activation depends on the suppression of RhoG by a previously uncharacterized ternary S4–synectin–RhoGDI1 protein complex and activation via PKCα.
APA, Harvard, Vancouver, ISO, and other styles
33

GANDHI, Payal N., Richard M. GIBSON, Xiaofeng TONG, Jun MIYOSHI, Yoshimi TAKAI, Martha KONIECZKOWSKI, John R. SEDOR, and Amy L. WILSON-DELFOSSE. "An activating mutant of Rac1 that fails to interact with Rho GDP-dissociation inhibitor stimulates membrane ruffling in mammalian cells." Biochemical Journal 378, no. 2 (March 1, 2004): 409–19. http://dx.doi.org/10.1042/bj20030979.

Full text
Abstract:
Rac1, a member of the Rho family of small GTP-binding proteins, is involved in the regulation of the actin cytoskeleton via activation of lamellipodia and membrane ruffle formation. RhoGDI (Rho-family-specific GDP-dissociation inhibitor) forms a complex with Rho proteins in the cytosol of mammalian cells. It not only regulates guanine nucleotide binding to Rho proteins, but may also function as a molecular shuttle to carry Rho proteins from an inactive cytosolic pool to the membrane for activation. These studies tested if RhoGDI is necessary for the translocation of Rac1 from the cytosol to the plasma membrane for the formation of membrane ruffles. We describe a novel mutant of Rac1, R66E (Arg66→Glu), that fails to bind RhoGDI. This RhoGDI-binding-defective mutation is combined with a Rac1-activating mutation G12V, resulting in a double-mutant [Rac1(G12V/R66E)] that fails to interact with RhoGDI in COS-7 cells, but remains constitutively activated. This double mutant stimulates membrane ruffling to a similar extent as that observed after epidermal growth factor treatment of non-transfected cells. To confirm that Rac1 can signal ruffle formation in the absence of interaction with RhoGDI, Rac1(G12V) was overexpressed in cultured mesangial cells derived from a RhoGDI knockout mouse. Rac1-mediated membrane ruffling was indistinguishable between the RhoGDI(−/−) and RhoGDI(+/+) cell lines. In both the COS-7 and cultured mesangial cells, Rac1(G12V) and Rac1(G12V/R66E) co-localize with membrane ruffles. These findings suggest that interaction with RhoGDI is not essential in the mechanism by which Rac1 translocates to the plasma membrane to stimulate ruffle formation.
APA, Harvard, Vancouver, ISO, and other styles
34

Dovas, Athanassios, and John R. Couchman. "RhoGDI: multiple functions in the regulation of Rho family GTPase activities." Biochemical Journal 390, no. 1 (August 9, 2005): 1–9. http://dx.doi.org/10.1042/bj20050104.

Full text
Abstract:
RhoGDI (Rho GDP-dissociation inhibitor) was identified as a down-regulator of Rho family GTPases typified by its ability to prevent nucleotide exchange and membrane association. Structural studies on GTPase–RhoGDI complexes, in combination with biochemical and cell biological results, have provided insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association–dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability and the importance of the particular membrane microenvironment that represents the site of action for GTPases. All these results point to a wider role for RhoGDI than initially perceived, making it a binding partner that can tightly control Rho GTPases, but which also allows them to reach their full spectrum of activities.
APA, Harvard, Vancouver, ISO, and other styles
35

Morin, Annie, Fabrice P. Cordelières, Jacqueline Cherfils, and Birgitta Olofsson. "RhoGDI3 and RhoG." Small GTPases 1, no. 3 (November 2010): 142–56. http://dx.doi.org/10.4161/sgtp.1.3.15112.

Full text
APA, Harvard, Vancouver, ISO, and other styles
36

Agarwal, Nitin K., Dubek Kazyken, and Dos D. Sarbassov. "Rictor encounters RhoGDI2." Small GTPases 4, no. 2 (April 2013): 102–5. http://dx.doi.org/10.4161/sgtp.23346.

Full text
APA, Harvard, Vancouver, ISO, and other styles
37

Abramovici, Hanan, Parmiss Mojtabaie, Robin J. Parks, Xiao-Ping Zhong, Gary A. Koretzky, Matthew K. Topham, and Stephen H. Gee. "Diacylglycerol Kinase ζ Regulates Actin Cytoskeleton Reorganization through Dissociation of Rac1 from RhoGDI." Molecular Biology of the Cell 20, no. 7 (April 2009): 2049–59. http://dx.doi.org/10.1091/mbc.e07-12-1248.

Full text
Abstract:
Activation of Rac1 GTPase signaling is stimulated by phosphorylation and release of RhoGDI by the effector p21-activated kinase 1 (PAK1), but it is unclear what initiates this potential feed-forward mechanism for regulation of Rac activity. Phosphatidic acid (PA), which is produced from the lipid second messenger diacylglycerol (DAG) by the action of DAG kinases (DGKs), is known to activate PAK1. Here, we investigated whether PA produced by DGKζ initiates RhoGDI release and Rac1 activation. In DGKζ-deficient fibroblasts PAK1 phosphorylation and Rac1–RhoGDI dissociation were attenuated, leading to reduced Rac1 activation after platelet-derived growth factor stimulation. The cells were defective in Rac1-regulated behaviors, including lamellipodia formation, membrane ruffling, migration, and spreading. Wild-type DGKζ, but not a kinase-dead mutant, or addition of exogenous PA rescued Rac activation. DGKζ stably associated with PAK1 and RhoGDI, suggesting these proteins form a complex that functions as a Rac1-selective RhoGDI dissociation factor. These results define a pathway that links diacylglycerol, DGKζ, and PA to the activation of Rac1: the PA generated by DGKζ activates PAK1, which dissociates RhoGDI from Rac1 leading to changes in actin dynamics that facilitate the changes necessary for cell motility.
APA, Harvard, Vancouver, ISO, and other styles
38

GIBSON, Richard M., and Amy L. WILSON-DELFOSSE. "RhoGDI-binding-defective mutant of Cdc42Hs targets to membranes and activates filopodia formation but does not cycle with the cytosol of mammalian cells." Biochemical Journal 359, no. 2 (October 8, 2001): 285–94. http://dx.doi.org/10.1042/bj3590285.

Full text
Abstract:
We have identified a mutant of the human G-protein Cdc42Hs, R66E, that fails to form a detectable complex with the GDP-dissociation inhibitor RhoGDI in cell-free systems or in intact cells. This point mutant is prenylated, binds guanine nucleotide and interacts with GTPase-activating protein in a manner indistinguishable from wild-type Cdc42Hs. Immunofluorescence localization studies revealed that this RhoGDI-binding-defective mutant is found predominantly in the Golgi apparatus, with a staining pattern similar to that of the wild-type protein. However, unlike wild-type Cdc42Hs, which is distributed in both the microsomal membrane and cytosolic fractions, studies using differential centrifugation show that prenylated R66E Cdc42Hs is found exclusively in association with lipid bilayers. Additionally, whereas the overexpression of RhoGDI results in an apparent translocation of wild-type Cdc42Hs from the Golgi apparatus into the cytosol, identical RhoGDI-overexpression conditions do not alter the Golgi localization of the R66E mutant. Furthermore, overexpression of this RhoGDI-binding-defective mutant of Cdc42Hs seems to activate redistribution of the actin cytoskeleton and filopodia formation in fibroblasts in a manner indistinguishable from the wild-type protein. Taken together, these results suggest that the interaction of Cdc42Hs with RhoGDI is not essential for proper membrane targeting of nascent prenylated Cdc42Hs in mammalian cells; neither is this interaction an essential part of the mechanism by which Cdc42Hs activates filopodia formation. However, it does seem that redistribution of Cdc42Hs to the cytosolic compartment is absolutely dependent on RhoGDI interaction.
APA, Harvard, Vancouver, ISO, and other styles
39

Reyes, Steve B., Anjana S. Narayanan, Hye Shin Lee, Jeremy H. Tchaicha, Kenneth D. Aldape, Frederick F. Lang, Kimberly F. Tolias, and Joseph H. McCarty. "αvβ8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion." Molecular Biology of the Cell 24, no. 4 (February 15, 2013): 474–82. http://dx.doi.org/10.1091/mbc.e12-07-0521.

Full text
Abstract:
The malignant brain cancer glioblastoma multiforme (GBM) displays invasive growth behaviors that are regulated by extracellular cues within the neural microenvironment. The adhesion and signaling pathways that drive GBM cell invasion remain largely uncharacterized. Here we use human GBM cell lines, primary patient samples, and preclinical mouse models to demonstrate that integrin αvβ8 is a major driver of GBM cell invasion. β8 integrin is overexpressed in many human GBM cells, with higher integrin expression correlating with increased invasion and diminished patient survival. Silencing β8 integrin in human GBM cells leads to impaired tumor cell invasion due to hyperactivation of the Rho GTPases Rac1 and Cdc42. β8 integrin coimmunoprecipitates with Rho-GDP dissociation inhibitor 1 (RhoGDI1), an intracellular signaling effector that sequesters Rho GTPases in their inactive GDP-bound states. Silencing RhoGDI1 expression or uncoupling αvβ8 integrin–RhoGDI1 protein interactions blocks GBM cell invasion due to Rho GTPase hyperactivation. These data reveal for the first time that αvβ8 integrin, via interactions with RhoGDI1, regulates activation of Rho proteins to promote GBM cell invasiveness. Hence targeting the αvβ8 integrin–RhoGDI1 signaling axis might be an effective strategy for blocking GBM cell invasion.
APA, Harvard, Vancouver, ISO, and other styles
40

DerMardirossian, Céline, Gabriel Rocklin, Ji-Yeon Seo, and Gary M. Bokoch. "Phosphorylation of RhoGDI by Src Regulates Rho GTPase Binding and Cytosol-Membrane Cycling." Molecular Biology of the Cell 17, no. 11 (November 2006): 4760–68. http://dx.doi.org/10.1091/mbc.e06-06-0533.

Full text
Abstract:
Rho GTPases (Rac, Rho, and Cdc42) play important roles in regulating cell function through their ability to coordinate the actin cytoskeleton, modulate the formation of signaling reactive oxidant species, and control gene transcription. Activation of Rho GTPase signaling pathways requires the regulated release of Rho GTPases from RhoGDI complexes, followed by their reuptake after membrane cycling. We show here that Src kinase binds and phosphorylates RhoGDI both in vitro and in vivo at Tyr156. Analysis of Rho GTPase–RhoGDI complexes using in vitro assays of complexation and in vivo by coimmunoprecipitation analysis indicates that Src-mediated phosphorylation of Tyr156 causes a dramatic decrease in the ability of RhoGDI to form a complex with RhoA, Rac1, or Cdc42. Phosphomimetic mutation of Tyr156→Glu results in the constitutive association of RhoGDIY156E with the plasma membrane and/or associated cortical actin. Substantial cortical localization of tyrosine-phosphorylated RhoGDI is also observed in fibroblasts expressing active Src, where it is most evident in podosomes and regions of membrane ruffling. Expression of membrane-localized RhoGDIY156E mutant is associated with enhanced cell spreading and membrane ruffling. These results suggest that Src-mediated RhoGDI phosphorylation is a novel physiological mechanism for regulating Rho GTPase cytosol membrane–cycling and activity.
APA, Harvard, Vancouver, ISO, and other styles
41

Lee, Hye Shin, Mujeeburahiman Cheerathodi, Sankar P. Chaki, Steve B. Reyes, Yanhua Zheng, Zhimin Lu, Helena Paidassi, et al. "Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells." Molecular and Cellular Biology 35, no. 8 (February 9, 2015): 1401–13. http://dx.doi.org/10.1128/mcb.00112-15.

Full text
Abstract:
Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells.
APA, Harvard, Vancouver, ISO, and other styles
42

FORGET, Marie-Annick, Richard R. DESROSIERS, Denis GINGRAS, and Richard BÉLIVEAU. "Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes." Biochemical Journal 361, no. 2 (January 8, 2002): 243–54. http://dx.doi.org/10.1042/bj3610243.

Full text
Abstract:
The Rho GDP dissociation inhibitor (RhoGDI) regulates the activation—inactivation cycle of Rho small GTPases, such as Cdc42 and RhoA, by extracting them from the membrane. To study the roles of Mg2+, phosphatidylinositol 4,5-bisphosphate (PIP2), ionic strength and phosphorylation on the interactions of RhoGDI with Cdc42 and RhoA, we developed a new, efficient and reliable method to produce prenylated Rho proteins using the yeast Saccharomyces cerevisiae. It has been previously reported that protein kinase A (PKA)-treatment of isolated membranes increased RhoA extraction from membranes by RhoGDI [Lang, Gesbert, Delespine-Carmagnat, Stancou, Pouchelet and Bertoglio (1996) EMBO J. 16, 510–519]. In the present study, we used an in vitro affinity chromatography system to show that phosphorylation of RhoA and Cdc42 significantly increased their interaction with RhoGDI under physiological conditions of ionic strength. This increase was independent of the nucleotide (GDP or guanosine 5′-[γ-thio]triphosphate) loaded on to the Rho proteins, as well as of Mg2+ and PIP2. Moreover, dephosphorylation of rat brain membranes by alkaline phosphatase significantly decreased the extraction of RhoA and Cdc42 by RhoGDI. Subsequent re-phosphorylation by PKA restored the extraction levels, indicating the reversibility of this process. These results clearly demonstrate that the phosphorylation states of Cdc42 and RhoA regulate their interactions with RhoGDI and, consequently, their extraction from rat brain membranes. We therefore suggest that phosphorylation is a mechanism of regulation of Cdc42 and RhoA activity that is independent of GDP—GTP cycling.
APA, Harvard, Vancouver, ISO, and other styles
43

Ueyama, Takehiko, Jeonghyun Son, Takeshi Kobayashi, Takeshi Hamada, Takashi Nakamura, Hirofumi Sakaguchi, Toshihiko Shirafuji, and Naoaki Saito. "Negative Charges in the Flexible N-Terminal Domain of Rho GDP-Dissociation Inhibitors (RhoGDIs) Regulate the Targeting of the RhoGDI–Rac1 Complex to Membranes." Journal of Immunology 191, no. 5 (August 5, 2013): 2560–69. http://dx.doi.org/10.4049/jimmunol.1300209.

Full text
APA, Harvard, Vancouver, ISO, and other styles
44

Ard, Ryan, Kirk Mulatz, Hanan Abramovici, Jean-Christian Maillet, Alexandra Fottinger, Tanya Foley, Michèle-Renée Byham, et al. "Diacylglycerol kinase ζ regulates RhoA activation via a kinase-independent scaffolding mechanism." Molecular Biology of the Cell 23, no. 20 (October 15, 2012): 4008–19. http://dx.doi.org/10.1091/mbc.e12-01-0026.

Full text
Abstract:
Rho GTPases share a common inhibitor, Rho guanine nucleotide dissociation inhibitor (RhoGDI), which regulates their expression levels, membrane localization, and activation state. The selective dissociation of individual Rho GTPases from RhoGDI ensures appropriate responses to cellular signals, but the underlying mechanisms are unclear. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, selectively dissociates Rac1 by stimulating PAK1-mediated phosphorylation of RhoGDI on Ser-101/174. Similarly, phosphorylation of RhoGDI on Ser-34 by protein kinase Cα (PKCα) selectively releases RhoA. Here we show DGKζ is required for RhoA activation and Ser-34 phosphorylation, which were decreased in DGKζ-deficient fibroblasts and rescued by wild-type DGKζ or a catalytically inactive mutant. DGKζ bound directly to the C-terminus of RhoA and the regulatory arm of RhoGDI and was required for efficient interaction of PKCα and RhoA. DGKζ-null fibroblasts had condensed F-actin bundles and altered focal adhesion distribution, indicative of aberrant RhoA signaling. Two targets of the RhoA effector ROCK showed reduced phosphorylation in DGKζ-null cells. Collectively our findings suggest DGKζ functions as a scaffold to assemble a signaling complex that functions as a RhoA-selective, GDI dissociation factor. As a regulator of Rac1 and RhoA activity, DGKζ is a critical factor linking changes in lipid signaling to actin reorganization.
APA, Harvard, Vancouver, ISO, and other styles
45

Larsen, Anna K., René Lametsch, John S. Elce, Jørgen K. Larsen, Bo Thomsen, Martin R. Larsen, Moira A. Lawson, Peter A. Greer, and Per Ertbjerg. "Genetic disruption of calpain correlates with loss of membrane blebbing and differential expression of RhoGDI-1, cofilin and tropomyosin." Biochemical Journal 411, no. 3 (April 14, 2008): 657–66. http://dx.doi.org/10.1042/bj20070522.

Full text
Abstract:
Dynamic regulation of the actin cytoskeleton is important for cell motility, spreading and the formation of membrane surface extensions such as lamellipodia, ruffles and blebs. The ubiquitous calpains contribute to integrin-mediated cytoskeletal remodelling during cell migration and spreading, by cleavage of focal adhesion components and signalling molecules. In the present study, the live-cell morphology of calpain-knockout and wild-type cells was examined by time-lapse fluorescence microscopy, and a role of calpain in mediating the formation of sporadic membrane blebs was established. Membrane blebbing was significantly reduced in calpain-knockout cells, and genetic rescue fully restored the wild-type phenotype in knockout cells. Proteomic comparison of wild-type and knockout cells identified decreased levels of RhoGDI-1 (Rho GDP-dissociation inhibitor) and cofilin 1, and increased levels of tropomyosin in calpain-knockout cells, suggesting a role of calpain in regulating membrane extensions involving these proteins. RhoGDI, cofilin and tropomyosin are known regulators of actin filament dynamics and membrane extensions. The reduced levels of RhoGDI-1 in calpain-knockout cells observed by proteome analysis were confirmed by immunoblotting. Genetic rescue of the calpain-knockout cells enhanced RhoGDI-1-expression 2-fold above that normally present in wild-type cells. These results suggest a regulatory connection between calpain and RhoGDI-1 in promoting formation of membrane blebs.
APA, Harvard, Vancouver, ISO, and other styles
46

Longenecker, Kenton, Paul Read, Urszula Derewenda, Zbigniew Dauter, Xiaopu Liu, Sarah Garrard, Lori Walker, et al. "How RhoGDI binds Rho." Acta Crystallographica Section D Biological Crystallography 55, no. 9 (September 1, 1999): 1503–15. http://dx.doi.org/10.1107/s090744499900801x.

Full text
Abstract:
Like all Rho (Ras homology) GTPases, RhoA functions as a molecular switch in cell signaling, alternating between GTP- and GDP-bound states, with its biologically inactive GDP-bound form maintained as a cytosolic complex with RhoGDI (guanine nucleotide-exchange inhibitor). The crystal structures of RhoA–GDP and of the C-terminal immunoglobulin-like domain of RhoGDI (residues 67–203) are known, but the mechanism by which the two proteins interact is not known. The functional human RhoA–RhoGDI complex has been expressed in yeast and crystallized (P6522, unit-cell parameters a = b = 139, c = 253 Å, two complexes in the asymmetric unit). Although diffraction from these crystals extends to 3.5 Å and is highly anisotropic, the experimentally phased (MAD plus MIR) electron-density map was adequate to reveal the mutual disposition of the two molecules. The result was validated by molecular-replacement calculations when data were corrected for anisotropy. Furthermore, the N-terminus of RhoGDI (the region involved in inhibition of nucleotide exchange) can be identified in the electron-density map: it is bound to the switch I and switch II regions of RhoA, occluding an epitope which binds Dbl-like nucleotide-exchange factors. The entrance of the hydrophobic pocket of RhoGDI is 25 Å from the last residue in the RhoA model, with its C-terminus oriented to accommodate the geranylgeranyl group without conformational change in RhoA.
APA, Harvard, Vancouver, ISO, and other styles
47

Boivin, D., and R. Beliveau. "Subcellular distribution and membrane association of Rho-related small GTP-binding proteins in kidney cortex." American Journal of Physiology-Renal Physiology 269, no. 2 (August 1, 1995): F180—F189. http://dx.doi.org/10.1152/ajprenal.1995.269.2.f180.

Full text
Abstract:
We have examined the subcellular distribution of Rho-related small GTP-binding proteins in the kidney. RhoA, CDC42, and Rac1 small GTP-binding proteins were found to be expressed at high levels in rat outer kidney cortex. Western blot analysis showed that these proteins were predominantly associated with brush-border and basolateral plasma membranes, with the exception of Rac1 which was localized predominantly in the mitochondria. RhoA and CDC42 were also found in the cytosol, and a small fraction was associated with cytoskeletal elements. A GDP-dissociation inhibitor specific for the Rho family (RhoGDI) was also identified and found to be located exclusively in the cytosol. Upon fractionation of kidney cytosol with anion-exchange chromatography, RhoA and CDC42 proteins eluted in two major well-resolved peaks that coeluted with the RhoGDI protein, suggesting that they form heterodimers. Association of RhoA and CDC42 with RhoGDI was further suggested by coelution of these proteins with RhoGDI at an estimated size of approximately 45 kDa after gel-filtration chromatography. However, a second peak of RhoA eluted as a 20-kDa protein, indicating that not all RhoA is complexed to RhoGDI. Addition of RhoA- and CDC42-enriched fractions to purified membranes from kidney cortex resulted in their translocation to the membranes and their carboxyl methylation. Both processes were stimulated by guanosine 5'-O-(3-thiotriphosphate). Methylation inhibitors had no effect on the translocation of RhoA to membranes, suggesting that this covalent modification is not required for association to the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
APA, Harvard, Vancouver, ISO, and other styles
48

Hatakeyama, J., S. Fukumoto, T. Nakamura, N. Haruyama, S. Suzuki, Y. Hatakeyama, L. Shum, C. W. Gibson, Y. Yamada, and A. B. Kulkarni. "Synergistic Roles of Amelogenin and Ameloblastin." Journal of Dental Research 88, no. 4 (April 2009): 318–22. http://dx.doi.org/10.1177/0022034509334749.

Full text
Abstract:
Amelogenin and ameloblastin, the major enamel matrix proteins, are important for enamel mineralization. To identify their synergistic roles in enamel development, we generated Amel X −/− /Ambn −/− mice. These mice showed additional enamel defects in comparison with Amel X −/− or Ambn −/− mice. In 7-day-old Amel X −/− /Ambn −/− mice, not only was the ameloblast layer irregular and detached from the enamel surface, as in Ambn −/−, but also, the enamel width was significantly reduced in the double-null mice as compared with Amel X −/− or Ambn −/− mice. Proteomic analysis of the double-null teeth revealed increased levels of RhoGDI (Arhgdia), a Rho-family-specific guanine nucleotide dissociation inhibitor, which is involved in important cellular processes, such as cell attachment. Both Amel X −/− /Ambn −/− mice and Ambn −/− mice displayed positive staining with RhoGDI antibody in the irregularly shaped ameloblasts detached from the matrix. Ameloblastin-regulated expression of RhoGDI suggests that Rho-mediated signaling pathway might play a role in enamel formation.
APA, Harvard, Vancouver, ISO, and other styles
49

Griner, Erin M., and Dan Theodorescu. "The faces and friends of RhoGDI2." Cancer and Metastasis Reviews 31, no. 3-4 (June 21, 2012): 519–28. http://dx.doi.org/10.1007/s10555-012-9376-6.

Full text
APA, Harvard, Vancouver, ISO, and other styles
50

Fujihara, Hideyoshi, Lori A. Walker, Ming Cui Gong, Emmanuel Lemichez, Patrice Boquet, Avril V. Somlyo, and Andrew P. Somlyo. "Inhibition of RhoA Translocation and Calcium Sensitization by In Vivo ADP-Ribosylation with the Chimeric Toxin DC3B." Molecular Biology of the Cell 8, no. 12 (December 1997): 2437–47. http://dx.doi.org/10.1091/mbc.8.12.2437.

Full text
Abstract:
Pretreatment of intact rabbit portal vein smooth muscle with the chimeric toxin DC3B (10−6 M, 48 h; Aullo et al., 1993 ; Boquet et al. 1995 ) ADP-ribosylated endogenous RhoA, including cytosolic RhoA complexed with rhoGDI, and inhibited the tonic phase of phenylephrine-induced contraction and the Ca2+-sensitization of force by phenylephrine, endothelin and guanosine triphosphate (GTP)γS, but did not inhibit Ca2+-sensitization by phorbol dibutyrate. DC3B also inhibited GTPγS-induced translocation of cytosolic RhoA ( Gonget al., 1997a ) to the membrane fraction. In DC3B-treated muscles the small fraction of membrane-associated RhoA could be immunoprecipitated, even after exposure to GTPγS, which prevents immunoprecipitation of non-ADP–ribosylated RhoA. Dissociation of cytosolic RhoA–rhoGDI complexes with SDS restored the immunoprecipitability and ADP ribosylatability of RhoA, indicating that both the ADP-ribosylation site (Asn 41) and RhoA insert loop ( Weiet al., 1997 ) are masked by rhoGDI and that the long axes of the two proteins are in parallel in the heterodimer. We conclude that RhoA plays a significant role in G-protein-, but not protein kinase C-mediated, Ca2+ sensitization and that ADP ribosylation inhibits in vivo the Ca2+-sensitizing effect of RhoA by interfering with its binding to a membrane-associated effector.
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the bibliographies on the topic 'RhoGDIα' for other source types:
Dissertations / Theses
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography