Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

Mark R Morgan, Hellyeh Hamidi, Mark D Bass, Stacey Warwood, Christoph Ballestrem, Martin J Humphries

Research output: Contribution to journalArticle (Academic Journal)

76 Citations (Scopus)

Abstract

Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of α5β1 and αVβ3 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 αVβ3 to the plasma membrane at the expense of α5β1. The resultant elevation in αVβ3 engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of α5β1, 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.
Original languageEnglish
Pages (from-to)472-85
Number of pages14
JournalDevelopmental Cell
Volume24
Issue number5
Early online date28 Feb 2013
DOIs
Publication statusPublished - 11 Mar 2013

Bibliographical note

Copyright © 2013 Elsevier Inc. All rights reserved.

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    Morgan, M. R., Hamidi, H., Bass, M. D., Warwood, S., Ballestrem, C., & Humphries, M. J. (2013). Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling. Developmental Cell, 24(5), 472-85. https://doi.org/10.1016/j.devcel.2013.01.027