A1 Refereed original research article in a scientific journal
Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling
Authors: Morgan MR, Hamidi H, Bass MD, Warwood S, Ballestrem C, Humphries MJ
Publisher: CELL PRESS
Publication year: 2013
Journal: Developmental Cell
Journal name in source: DEVELOPMENTAL CELL
Journal acronym: DEV CELL
Volume: 24
Issue: 5
First page : 472
Last page: 485
Number of pages: 14
ISSN: 1534-5807
DOI: https://doi.org/10.1016/j.devcel.2013.01.027
Abstract
Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of alpha(5)beta(1), and alpha(V)beta(3) integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of alpha(V)beta(3) to the plasma membrane at the expense of alpha(5)beta(1). The resultant elevation in alpha(V)beta(3) engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of alpha(5)beta(1), destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration.
Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of alpha(5)beta(1), and alpha(V)beta(3) integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of alpha(V)beta(3) to the plasma membrane at the expense of alpha(5)beta(1). The resultant elevation in alpha(V)beta(3) engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of alpha(5)beta(1), destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration.
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