Vav GEFs regulate macrophage morphology and adhesion-induced Rac and Rho activation.
The Vav family of proteins have the potential to act as both signalling adapters and GEFs for Rho GTPases. They have therefore been proposed as regulators of the cytoskeleton in various cell types. We have used macrophages from mice deficient in all three Vav isoforms to determine how their function affects cell morphology and migration. Macrophages lacking Vav proteins adopt an elongated morphology and have enhanced migratory persistence in culture. To investigate the pathways through which Vav proteins exert their effects we analysed the responses of macrophages to the chemoattractant CSF-1 and to adhesion. We found that morphological and signalling responses of macrophages to CSF-1 did not require Vav proteins. In contrast, adhesion-induced cell spreading, RhoA and Rac1 activation and cell signalling were all dependent on Vav proteins. We propose that Vav proteins affect macrophage morphology and motile behaviour by coupling adhesion receptors to Rac1 and RhoA activity and regulating adhesion signalling events such as paxillin and ERK1/2 phosphorylation by acting as adapters.
Bhavsar
Parag J
PJ
King's College London, Randall Division of Cell and Molecular Biophysics, Guy's Campus, London, UK.
Vigorito
Elena
E
Turner
Martin
M
Ridley
Anne J
AJ
D000818:Animals; D002448:Cell Adhesion; D048430:Cell Shape; D002478:Cells, Cultured; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms; D051567:Proto-Oncogene Proteins c-vav / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D020033:Protein Isoforms; D051567:Proto-Oncogene Proteins c-vav; C496619:Vav1 protein, mouse; C496622:Vav3 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins