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- Title
α4β< sub>1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with α4-cytoplasmic domain.
- Authors
Alon, Ronen; Feigelson, Sara W.; Manevich, Eugenia; Rose, David M.; Schmitz, Julia; Overby, Darryl R.; Winter, Eitan; Grabovsky, Valentin; Shinder, Vera; Matthews, Benjamin D.; Sokolovsky-Eisenberg, Maya; Ingber, Donald E.; Benoit, Martin; Ginsberg, Mark H.
- Abstract
The capacity of integrins to mediate adhesiveness is modulated by their cytoplasmic associations. In this study, we describe a novel mechanism by which α4-integrin adhesiveness is regulated by the cytoskeletal adaptor paxillin. A mutation of the α4 tail that disrupts paxillin binding, α4 (Y991A), reduced talin association to the α4β1 heterodimer, impaired integrin anchorage to the cytoskeleton, and suppressed α4β1-dependent capture and adhesion strengthening of Jurkat T cells to VCAM-1 under shear stress. The mutant retained intrinsic avidity to soluble or bead-immobilized VCAM-1, supported normal cell spreading at short-lived contacts, had normal α4-microvillar distribution, and responded to inside-out signals. This is the first demonstration that cytoskeletal anchorage of an integrin enhances the mechanical stability of its adhesive bonds under strain and, thereby, promotes its ability to mediate leukocyte adhesion under physiological shear stress conditions.
- Publication
Journal of Cell Biology, 2005, Vol 171, Issue 6, p1073
- ISSN
0021-9525
- Publication type
Academic Journal
- DOI
10.1083/jcb.200503155