p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling

Barberis, D., Casazza, A., Sordella, R., Corso, S., Artigiani, S., Settleman, J., Comoglio, P. M., Tamagnone, L. (October 2005) p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling. Journal of Cell Science, 118 (Pt 20). pp. 4689-700. ISSN 0021-9533

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URL: http://www.ncbi.nlm.nih.gov/pubmed/16188938
DOI: 10.1242/jcs.02590

Abstract

Plexins are transmembrane receptors for semaphorins, guiding cell migration and axon extension. Plexin activation leads to the disassembly of integrin-based focal adhesive structures and to actin cytoskeleton remodelling and inhibition of cell migration; however, the underlying molecular mechanisms are unclear. We consistently observe a transient decrease of cellular RhoA-GTP levels upon plexin activation in adherent cells. One of the main effectors of RhoA downregulation is p190, a ubiquitously expressed GTPase activating protein (GAP). We show that, in p190-deficient fibroblasts, the typical functional activities mediated by plexins (such as cell collapse and inhibition of integrin-based adhesion) are blocked or greatly impaired. Notably, the functional response can be rescued in these cells by re-expressing exogenous p190, but not a mutant form specifically lacking RhoGAP activity. We furthermore demonstrate that semaphorin function is blocked in epithelial cells, primary endothelial cells and neuroblasts upon treatment with small interfering RNAs that knockdown p190 expression. Finally, we show that p190 transiently associates with plexins, and its RhoGAP activity is increased in response to semaphorin stimulation. We conclude that p190-RhoGAP is crucially involved in semaphorin signalling to the actin cytoskeleton, via interaction with plexins.

Item Type: Paper
Uncontrolled Keywords: Animals Antigens, CD pharmacology Carrier Proteins metabolism Cell Adhesion drug effects Cell Movement drug effects Chemotaxis DNA-Binding Proteins Down-Regulation genetics Endothelial Cells cytology Epithelial Cells cytology drug effects Fibroblasts cytology drug effects Focal Adhesions GTPase-Activating Proteins metabolism Guanine Nucleotide Exchange Factors Humans Intracellular Signaling Peptides and Proteins Mice NIH 3T3 Cells Nerve Growth Factor pharmacology Neurites PC12 Cells Protein Binding RNA, Small Interfering genetics Rats Receptors, Cell Surface metabolism Repressor Proteins Semaphorins metabolism pharmacologRHo Signal Transduction
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > actin
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell

organs, tissues, organelles, cell types and functions > tissues types and functions > membranes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL labs > Sordella lab
Depositing User: CSHL Librarian
Date: 15 October 2005
Date Deposited: 17 Jan 2012 16:06
Last Modified: 13 Mar 2013 16:00
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22532

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