Increased spreading, Rac/p21-activated kinase (PAK) activity, and compromised cell motility in cells deficient in vasodilator-stimulated phosphoprotein (VASP).
Ena/VASP (Drosophila Enabled/vasodilator-stimulated phosphoprotein) proteins are key regulators that promote or inhibit actin-based motility, cell adhesion, and various aspects of axon guidance. However, a conclusive concept of Ena/VASP functions remains elusive. Here, we report that VASP-deficient fibroblasts, despite normal mammalian Enabled (Mena) and Ena-VASP-like (Evl) expression levels, are highly spread. VASP(-/-) cells cover about twice the substrate surface area as wild type cells, while cell volumes are unchanged. In accordance with these observations, activation of the Rac/p21-activated kinase (PAK) pathway, a crucial element in the regulation of cell spreading, is markedly enhanced in VASP(-/-) cells. Thus, in the absence of VASP Rac activation is dramatically prolonged, and PAK activity is elevated after stimulation with platelet-derived growth factor or serum, respectively. Moreover, VASP-deficient cells show compromised migration and reorientation in a wound healing assay. Collectively, our results reveal a VASP-dependent modulation of the Rac/PAK pathway and Rac/PAK-regulated processes, like cell motility and polarization.
García Arguinzonis
Maísa I
MI
Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Germany.
Galler
Annette B
AB
Walter
Ulrich
U
Reinhard
Matthias
M
Simm
Andreas
A
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size; D003598:Cytoskeletal Proteins; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; C102177:Evl protein, mouse; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011506:Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein; C515905:Pak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins