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The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration

Caveolin-1 (Cav1), a major Src kinase substrate phosphorylated on tyrosine-14 (Y14), contains the highly conserved membrane-proximal caveolin scaffolding domain (CSD; amino acids 82–101). Here we show, using CSD mutants (F92A/V94A) and membrane-permeable CSD-competing peptides, that Src kinase–depen...

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Autores principales: Meng, Fanrui, Saxena, Sandeep, Liu, Youtao, Joshi, Bharat, Wong, Timothy H., Shankar, Jay, Foster, Leonard J., Bernatchez, Pascal, Nabi, Ivan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531735/
https://www.ncbi.nlm.nih.gov/pubmed/28592633
http://dx.doi.org/10.1091/mbc.E17-05-0278
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author Meng, Fanrui
Saxena, Sandeep
Liu, Youtao
Joshi, Bharat
Wong, Timothy H.
Shankar, Jay
Foster, Leonard J.
Bernatchez, Pascal
Nabi, Ivan R.
author_facet Meng, Fanrui
Saxena, Sandeep
Liu, Youtao
Joshi, Bharat
Wong, Timothy H.
Shankar, Jay
Foster, Leonard J.
Bernatchez, Pascal
Nabi, Ivan R.
author_sort Meng, Fanrui
collection PubMed
description Caveolin-1 (Cav1), a major Src kinase substrate phosphorylated on tyrosine-14 (Y14), contains the highly conserved membrane-proximal caveolin scaffolding domain (CSD; amino acids 82–101). Here we show, using CSD mutants (F92A/V94A) and membrane-permeable CSD-competing peptides, that Src kinase–dependent pY14Cav1 regulation of focal adhesion protein stabilization, focal adhesion tension, and cancer cell migration is CSD dependent. Quantitative proteomic analysis of Cav1-GST (amino acids 1–101) pull downs showed sixfold-increased binding of vinculin and, to a lesser extent, α-actinin, talin, and filamin, to phosphomimetic Cav1Y14D relative to nonphosphorylatable Cav1Y14F. Consistently, pY14Cav1 enhanced CSD-dependent vinculin tension in focal adhesions, dampening force fluctuation and synchronously stabilizing cellular focal adhesions in a high-tension mode, paralleling effects of actin stabilization. This identifies pY14Cav1 as a molecular regulator of focal adhesion tension and suggests that functional interaction between Cav1 Y14 phosphorylation and the CSD promotes focal adhesion traction and, thereby, cancer cell motility.
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spelling pubmed-55317352017-10-16 The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration Meng, Fanrui Saxena, Sandeep Liu, Youtao Joshi, Bharat Wong, Timothy H. Shankar, Jay Foster, Leonard J. Bernatchez, Pascal Nabi, Ivan R. Mol Biol Cell Articles Caveolin-1 (Cav1), a major Src kinase substrate phosphorylated on tyrosine-14 (Y14), contains the highly conserved membrane-proximal caveolin scaffolding domain (CSD; amino acids 82–101). Here we show, using CSD mutants (F92A/V94A) and membrane-permeable CSD-competing peptides, that Src kinase–dependent pY14Cav1 regulation of focal adhesion protein stabilization, focal adhesion tension, and cancer cell migration is CSD dependent. Quantitative proteomic analysis of Cav1-GST (amino acids 1–101) pull downs showed sixfold-increased binding of vinculin and, to a lesser extent, α-actinin, talin, and filamin, to phosphomimetic Cav1Y14D relative to nonphosphorylatable Cav1Y14F. Consistently, pY14Cav1 enhanced CSD-dependent vinculin tension in focal adhesions, dampening force fluctuation and synchronously stabilizing cellular focal adhesions in a high-tension mode, paralleling effects of actin stabilization. This identifies pY14Cav1 as a molecular regulator of focal adhesion tension and suggests that functional interaction between Cav1 Y14 phosphorylation and the CSD promotes focal adhesion traction and, thereby, cancer cell motility. The American Society for Cell Biology 2017-08-01 /pmc/articles/PMC5531735/ /pubmed/28592633 http://dx.doi.org/10.1091/mbc.E17-05-0278 Text en © 2017 Meng 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 for Cell Biology.
spellingShingle Articles
Meng, Fanrui
Saxena, Sandeep
Liu, Youtao
Joshi, Bharat
Wong, Timothy H.
Shankar, Jay
Foster, Leonard J.
Bernatchez, Pascal
Nabi, Ivan R.
The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
title The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
title_full The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
title_fullStr The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
title_full_unstemmed The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
title_short The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
title_sort phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531735/
https://www.ncbi.nlm.nih.gov/pubmed/28592633
http://dx.doi.org/10.1091/mbc.E17-05-0278
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