αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration
Author(s)
Gertler, Frank; Worth, Daniel C.; Hodivala-Dilke, Kairbaan; Robinson, Stephen D.; King, Samantha J.; Morton, Penny E.; Humphries, Martin J.; Parsons, Maddy; ... Show more Show less
DownloadWorth-2010-alpha nu beta 3 inte.pdf (3.259Mb)
PUBLISHER_POLICY
Publisher Policy
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Alternative title
αvβ3 [alpha nu beta 3] integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration
Terms of use
Metadata
Show full item recordAbstract
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 β3 [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 β3 [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 β3 [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 β1 [beta 1] integrin. These data demonstrate a novel mechanism by which αvβ3 [alpha nu beta 3]integrin acts to locally suppress β1 [beta 1]integrin activation and regulate protrusion, adhesion dynamics, and persistent migration.
Date issued
2010-04Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MITJournal
Journal of Cell Biology
Publisher
Rockefeller University Press
Citation
Worth, D. C. et al. "αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.” The Journal of Cell Biology 189.2 (2010): 369-383.
Version: Final published version
ISSN
0021-9525
1540-8140