A role for WASP Interacting Protein, WIP, in fibroblast adhesion, spreading and migration.
The WASP (Wiskott Aldrich Syndrome Protein) Interacting Protein, WIP, regulates actin polymerization and the formation of actin-rich structures such as filopodia and lamellipodia, each of which is involved in cellular adhesion, spreading and migration. To define the role for WIP in these activities, we analysed cell adhesion and spreading as well as the redistribution of polymerised actin and paxillin that occurred when fibroblasts were plated onto different substrata. We compared the effect of WIP overexpression (gain of function) with that of WIP deficiency (loss of function) on these parameters. WIP-overexpression delayed cellular adhesion and spreading, an effect that could be compensated for by exposure to Y-27632, a well characterized ROCK (Rho kinase) inhibitor. WIP overexpression augmented the phosphorylation of Erk and JNK induced by binding to fibronectin, suggesting that WIP participates in signal transduction pathways initiated by integrin engagement. Conversely, WIP deficiency accelerated fibroblast adhesion to plastic and led to the formation of enlarged focal adhesions. The influence of WIP on fibroblast migration was measured by scratch assay. WIP-overexpression reduced migration while WIP-deficiency increased it, suggesting that WIP acts as a negative regulator of fibroblast migration. Together, these findings suggest a novel role for WIP in fibroblast adhesion, spreading and migration.
Lanzardo
Stefania
S
Università degli Studi di Torino, Orbassano 10043, TO, Italy.
Curcio
Claudia
C
Forni
Guido
G
Antón
Inés M
IM
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases
D000577:Amides; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C491671:Waspip protein, mouse; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases