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Two modes of integrin activation form a binary molecular switch in adhesion maturation

Talin-mediated integrin activation drives integrin-based adhesions. Here we examine the roles of two proteins that induce talin–integrin interactions—vinculin and Rap1-GTP-interacting adaptor molecule (RIAM)—in the formation and maturation of integrin-based adhesions. RIAM-containing adhesions are p...

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Autores principales: Lee, Ho-Sup, Anekal, Praju, Lim, Chinten James, Liu, Chi-Chao, Ginsberg, Mark H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639047/
https://www.ncbi.nlm.nih.gov/pubmed/23468527
http://dx.doi.org/10.1091/mbc.E12-09-0695
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author Lee, Ho-Sup
Anekal, Praju
Lim, Chinten James
Liu, Chi-Chao
Ginsberg, Mark H.
author_facet Lee, Ho-Sup
Anekal, Praju
Lim, Chinten James
Liu, Chi-Chao
Ginsberg, Mark H.
author_sort Lee, Ho-Sup
collection PubMed
description Talin-mediated integrin activation drives integrin-based adhesions. Here we examine the roles of two proteins that induce talin–integrin interactions—vinculin and Rap1-GTP-interacting adaptor molecule (RIAM)—in the formation and maturation of integrin-based adhesions. RIAM-containing adhesions are primarily in the lamellipodium; RIAM is subsequently reduced in mature focal adhesions due to direct competition with vinculin for talin-binding sites. We show that vinculin binding to talin induces Rap1-independent association of talin with integrins and resulting integrin activation, in sharp contrast to Rap1-dependent RIAM-induced activation. Vinculin stabilizes adhesions, increasing their ability to transmit force, whereas RIAM played a critical role in lamellipodial protrusion. Thus displacement of RIAM by vinculin acts as a molecular switch that mediates the transition of integrin-based adhesions from drivers of lamellipodial protrusion to stable, force-bearing adhesions. Consequently changes in the abundance of two multiprotein modules within maturing adhesions, one regulated by Rap1 and one by tension, result in the temporal evolution of adhesion functions.
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spelling pubmed-36390472013-07-16 Two modes of integrin activation form a binary molecular switch in adhesion maturation Lee, Ho-Sup Anekal, Praju Lim, Chinten James Liu, Chi-Chao Ginsberg, Mark H. Mol Biol Cell Articles Talin-mediated integrin activation drives integrin-based adhesions. Here we examine the roles of two proteins that induce talin–integrin interactions—vinculin and Rap1-GTP-interacting adaptor molecule (RIAM)—in the formation and maturation of integrin-based adhesions. RIAM-containing adhesions are primarily in the lamellipodium; RIAM is subsequently reduced in mature focal adhesions due to direct competition with vinculin for talin-binding sites. We show that vinculin binding to talin induces Rap1-independent association of talin with integrins and resulting integrin activation, in sharp contrast to Rap1-dependent RIAM-induced activation. Vinculin stabilizes adhesions, increasing their ability to transmit force, whereas RIAM played a critical role in lamellipodial protrusion. Thus displacement of RIAM by vinculin acts as a molecular switch that mediates the transition of integrin-based adhesions from drivers of lamellipodial protrusion to stable, force-bearing adhesions. Consequently changes in the abundance of two multiprotein modules within maturing adhesions, one regulated by Rap1 and one by tension, result in the temporal evolution of adhesion functions. The American Society for Cell Biology 2013-05-01 /pmc/articles/PMC3639047/ /pubmed/23468527 http://dx.doi.org/10.1091/mbc.E12-09-0695 Text en © 2013 Lee et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Lee, Ho-Sup
Anekal, Praju
Lim, Chinten James
Liu, Chi-Chao
Ginsberg, Mark H.
Two modes of integrin activation form a binary molecular switch in adhesion maturation
title Two modes of integrin activation form a binary molecular switch in adhesion maturation
title_full Two modes of integrin activation form a binary molecular switch in adhesion maturation
title_fullStr Two modes of integrin activation form a binary molecular switch in adhesion maturation
title_full_unstemmed Two modes of integrin activation form a binary molecular switch in adhesion maturation
title_short Two modes of integrin activation form a binary molecular switch in adhesion maturation
title_sort two modes of integrin activation form a binary molecular switch in adhesion maturation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639047/
https://www.ncbi.nlm.nih.gov/pubmed/23468527
http://dx.doi.org/10.1091/mbc.E12-09-0695
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