scholarly journals BIG1 Is a Binding Partner of Myosin IXb and Regulates Its Rho-GTPase Activating Protein Activity

2005 ◽  
Vol 280 (11) ◽  
pp. 10128-10134 ◽  
Author(s):  
Nobutaka Saeki ◽  
Hiroshi Tokuo ◽  
Mitsuo Ikebe
Keyword(s):  
Rho Gtpase ◽  
Gtpase Activating Protein ◽  
Protein Activity ◽  
Binding Partner

scholarly journals Structure-activity mapping of ARHGAP36 reveals regulatory roles for its GAP homology and C-terminal domains

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251684
Author(s):  
Patricia R. Nano ◽  
Taylor K. Johnson ◽  
Takamasa Kudo ◽  
Nancie A. Mooney ◽  
Jun Ni ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Signaling Proteins ◽  
Gtpase Activating Protein ◽  
Mutagenesis Screen ◽  
Binding Partner ◽  
Spinal Cord Development ◽  
Terminal Domain ◽  
Structure Activity ◽  
Truncation Mutant ◽  
Gli Transcription Factors

ARHGAP36 is an atypical Rho GTPase-activating protein (GAP) family member that drives both spinal cord development and tumorigenesis, acting in part through an N-terminal motif that suppresses protein kinase A and activates Gli transcription factors. ARHGAP36 also contains isoform-specific N-terminal sequences, a central GAP-like module, and a unique C-terminal domain, and the functions of these regions remain unknown. Here we have mapped the ARHGAP36 structure-activity landscape using a deep sequencing-based mutagenesis screen and truncation mutant analyses. Using this approach, we have discovered several residues in the GAP homology domain that are essential for Gli activation and a role for the C-terminal domain in counteracting an N-terminal autoinhibitory motif that is present in certain ARHGAP36 isoforms. In addition, each of these sites modulates ARHGAP36 recruitment to the plasma membrane or primary cilium. Through comparative proteomics, we also have identified proteins that preferentially interact with active ARHGAP36, and we demonstrate that one binding partner, prolyl oligopeptidase-like protein, is a novel ARHGAP36 antagonist. Our work reveals multiple modes of ARHGAP36 regulation and establishes an experimental framework that can be applied towards other signaling proteins.

scholarly journals Rho GAP myosin IXa is a regulator of kidney tubule function

2015 ◽  
Vol 309 (6) ◽  
pp. F501-F513 ◽  
Author(s):  
Sabine Thelen ◽  
Marouan Abouhamed ◽  
Giuliano Ciarimboli ◽  
Bayram Edemir ◽  
Martin Bähler
Keyword(s):  
Structural Changes ◽  
Rho Gtpase ◽  
The Body ◽  
Gtpase Activating Protein ◽  
Protein Activity ◽  
Proximal Tubule Cells ◽  
Proximal Tubular ◽  
Protein Reabsorption ◽  
Genetic Deletion ◽  
Ciliated Epithelial Cells

Mammalian class IX myosin Myo9a is a single-headed, actin-dependent motor protein with Rho GTPase-activating protein activity that negatively regulates Rho GTPase signaling. Myo9a is abundantly expressed in ciliated epithelial cells of several organs. In mice, genetic deletion of Myo9a leads to the formation of hydrocephalus. Whether Myo9a also has essential functions in the epithelia of other organs of the body has not been explored. In the present study, we report that Myo9a-deficient mice develop bilateral renal disease, characterized by dilation of proximal tubules, calyceal dilation, and thinning of the parenchyma and fibrosis. These structural changes are accompanied by polyuria (with normal vasopressin levels) and low-molecular-weight proteinuria. Immunohistochemistry revealed that Myo9a is localized to the circumferential F-actin belt of proximal tubule cells. In kidneys lacking Myo9a, the multiligand binding receptor megalin and its ligand albumin accumulated at the luminal surface of Myo9a-deficient proximal tubular cells, suggesting that endocytosis is dysregulated. In addition, we found, surprisingly, that levels of murine diaphanous-related formin-1, a Rho effector, were decreased in Myo9a-deficient kidneys as well as in Myo9a knockdown LLC-PK1 cells. In summary, deletion of the Rho GTPase-activating protein Myo9a in mice causes proximal tubular dilation and fibrosis, and we speculate that downregulation of murine diaphanous-related formin-1 and impaired protein reabsorption contribute to the pathophysiology.

scholarly journals Effects of Structure of Rho GTPase-activating Protein DLC-1 on Cell Morphology and Migration

2008 ◽  
Vol 283 (47) ◽  
pp. 32762-32770 ◽  
Author(s):  
Tai Young Kim ◽  
Kevin D. Healy ◽  
Channing J. Der ◽  
Noah Sciaky ◽  
Yung-Jue Bang ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Rho Gtpase ◽  
Gtpase Activating Protein ◽  
And Migration

scholarly journals The BNIP-2 and Cdc42GAP Homology (BCH) Domain of p50RhoGAP/Cdc42GAP Sequesters RhoA from Inactivation by the Adjacent GTPase-activating Protein Domain

2010 ◽  
Vol 21 (18) ◽  
pp. 3232-3246 ◽  
Author(s):  
Yi Ting Zhou ◽  
Li Li Chew ◽  
Sheng-cai Lin ◽  
Boon Chuan Low
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Intramolecular Interaction ◽  
Complete Loss ◽  
Protein Domain ◽  
Binding Motif ◽  
Gtpase Activating Protein ◽  
New Paradigm ◽  
Cell Rounding ◽  
In Cis

The BNIP-2 and Cdc42GAP homology (BCH) domain is a novel regulator for Rho GTPases, but its impact on p50-Rho GTPase-activating protein (p50RhoGAP or Cdc42GAP) in cells remains elusive. Here we show that deletion of the BCH domain from p50RhoGAP enhanced its GAP activity and caused drastic cell rounding. Introducing constitutively active RhoA or inactivating GAP domain blocked such effect, whereas replacing the BCH domain with endosome-targeting SNX3 excluded requirement of endosomal localization in regulating the GAP activity. Substitution with homologous BCH domain from Schizosaccharomyces pombe, which does not bind mammalian RhoA, also led to complete loss of suppression. Interestingly, the p50RhoGAP BCH domain only targeted RhoA, but not Cdc42 or Rac1, and it was unable to distinguish between GDP and the GTP-bound form of RhoA. Further mutagenesis revealed a RhoA-binding motif (residues 85-120), which when deleted, significantly reduced BCH inhibition on GAP-mediated cell rounding, whereas its full suppression also required an intramolecular interaction motif (residues 169-197). Therefore, BCH domain serves as a local modulator in cis to sequester RhoA from inactivation by the adjacent GAP domain, adding to a new paradigm for regulating p50RhoGAP signaling.

scholarly journals Rho-GTPase activating-protein 18: a biomarker associated with good prognosis in invasive breast cancer

2017 ◽  
Vol 117 (8) ◽  
pp. 1176-1184 ◽  
Author(s):  
Mohammed A Aleskandarany ◽  
Sultan Sonbul ◽  
Rachel Surridge ◽  
Abhik Mukherjee ◽  
Carlos Caldas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Rho Gtpase ◽  
Good Prognosis ◽  
Gtpase Activating Protein

scholarly journals Secretory Pathway-Dependent Localization of the Saccharomyces cerevisiae Rho GTPase-Activating Protein Rgd1p at Growth Sites

2012 ◽  
Vol 11 (5) ◽  
pp. 590-600 ◽  
Author(s):  
Fabien Lefèbvre ◽  
Valérie Prouzet-Mauléon ◽  
Michel Hugues ◽  
Marc Crouzet ◽  
Aurélie Vieillemard ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Cell Cycle Progression ◽  
Secretory Pathway ◽  
Rho Gtpase ◽  
Secretory Vesicles ◽  
Gtpase Activating Protein ◽  
Content Type

ABSTRACT Establishment and maintenance of cell polarity in eukaryotes depends upon the regulation of Rho GTPases. In Saccharomyces cerevisiae , the Rho GTPase activating protein (RhoGAP) Rgd1p stimulates the GTPase activities of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. Consistent with the distribution of Rho3p and Rho4p, Rgd1p is found mostly in areas of polarized growth during cell cycle progression. Rgd1p was mislocalized in mutants specifically altered for Golgi apparatus-based phosphatidylinositol 4-P [PtdIns(4)P] synthesis and for PtdIns(4,5)P 2 production at the plasma membrane. Analysis of Rgd1p distribution in different membrane-trafficking mutants suggested that Rgd1p was delivered to growth sites via the secretory pathway. Rgd1p may associate with post-Golgi vesicles by binding to PtdIns(4)P and then be transported by secretory vesicles to the plasma membrane. In agreement, we show that Rgd1p coimmunoprecipitated and localized with markers specific to secretory vesicles and cofractionated with a plasma membrane marker. Moreover, in vivo imaging revealed that Rgd1p was transported in an anterograde manner from the mother cell to the daughter cell in a vectoral manner. Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck.

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