Src activation and translocation from focal adhesions to membrane ruffles contribute to formation of new adhesion sites.
Cell migration requires the coordinated turnover of focal adhesions, a process that involves FAK phosphorylation. Since Src is the major kinase implicated in FAK phosphorylation, we focus here on the role of Src activation on adhesion remodelling. In astrocytoma cells, constitutively activated Src induces both FAK phosphorylation and adhesion rearrangement. To evaluate how Src controls these processes, we used a recently described Src reporter to monitor the dynamics of Src phosphorylation. Upon Src activation, focal adhesions started to disassemble while Src appeared highly expressed at newly formed membrane ruffles. Kinetic analysis of time-lapse movies showed that loss of phospho-Src at focal adhesions was time-correlated with the appearance of membrane ruffles containing phospho-Src. Moreover, FLIP analysis revealed a dynamic equilibrium of Src between focal adhesions and membrane ruffles. We conclude that upon phosphorylation, Src is directly translocated from focal adhesions to membrane ruffles, thereby promoting formation of new adhesion complexes.
Hamadi
A
A
UMR CNRS 7175, Dépt. Pharmacologie et Physicochimie, Université Louis Pasteur - Strasbourg I, Faculté de Pharmacie, 74 rte du Rhin, BP 60024, 67401, Illkirch, France.
Deramaudt
T B
TB
Takeda
K
K
Rondé
P
P
D000818:Animals; D001254:Astrocytoma; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014638:Vanadates / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; C076715:pervanadate; D016596:Vinculin; D014638:Vanadates; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases