alpha nu beta 3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration

作者：Worth Daniel C; Hodivala Dilke Kairbaan; Robinson Stephen D; King Samantha J; Morton Penny E; Gertler Frank B; Humphries Martin J; Parsons Maddy^*

来源：The Journal of Cell Biology, 2010, 189(2): 369-383.

DOI：10.1083/jcb.200912014

Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of beta 3 integrin in fibroblasts results in enhanced focal adhesion turnover and migration speed but impaired directional motility on both 2D and 3D matrices. These motility defects are coupled with an increased rate of actin-based protrusion. Analysis of downstream signaling events reveals that loss of beta 3 integrin results in a loss of protein kinase A-dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in beta 3-null cells is preferentially associated with Rap1-GTP-interacting adaptor molecule (RIAM) both in vitro and in vivo, which leads to enhanced formation of a VASP-RIAM complex at focal adhesions and subsequent increased binding of talin to beta 1 integrin. These data demonstrate a novel mechanism by which alpha nu beta 3 integrin acts to locally suppress beta 1 integrin activation and regulate protrusion, adhesion dynamics, and persistent migration.

• 出版日期2010-4-19