alpha_4\beta_1-Dependent$ Adhesion Strengthening under Mechanical Strain Is Regulated by Paxillin Association with the $\alpha_4-Cytoplasmic$ Domain

The capacity of integrins to mediate adhesiveness is modulated by their cytoplasmic associations. In this study, we describe a novel mechanism by which $\alpha_4-integrin$ adhesiveness is regulated by the cytoskeletal adaptor paxillin. A mutation of the α4 tail that disrupts paxillin binding, $\alph...

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Veröffentlicht in:The Journal of cell biology 2005-12, Vol.171 (6), p.1073-1084
Hauptverfasser: 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.
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container_end_page 1084
container_issue 6
container_start_page 1073
container_title The Journal of cell biology
container_volume 171
creator 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.
description The capacity of integrins to mediate adhesiveness is modulated by their cytoplasmic associations. In this study, we describe a novel mechanism by which $\alpha_4-integrin$ adhesiveness is regulated by the cytoskeletal adaptor paxillin. A mutation of the α4 tail that disrupts paxillin binding, $\alpha_4(Y991A)$, reduced talin association to the α4β1 heterodimer, impaired integrin anchorage to the cytoskeleton, and suppressed $\alpha_4\beta_1-dependent$ 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 $\alpha_4-microvillar$ 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.
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subjects Adhesive bonding
Adhesives
Cell adhesion
Cytoskeleton
Integrins
Leukocytes
Ligands
Shear flow
Shear stress
T lymphocytes
title alpha_4\beta_1-Dependent$ Adhesion Strengthening under Mechanical Strain Is Regulated by Paxillin Association with the $\alpha_4-Cytoplasmic$ Domain
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