Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

Morgan, Mark R ORCID: 0000-0001-7728-9883, Hamidi, Hellyeh, Bass, Mark D, Warwood, Stacey, Ballestrem, Christoph and Humphries, Martin J (2013) Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling. DEVELOPMENTAL CELL, 24 (5). pp. 472-485.

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Official URL: http://dx.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 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.

Item Type:	Article
Additional Information:	## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords:	Cells, Cultured, Cell Membrane, Focal Adhesions, Cytosol, Fibroblasts, Humans, ADP-Ribosylation Factors, Tyrosine, Integrin alpha5beta1, Integrin alphaVbeta3, Fluorescent Antibody Technique, Blotting, Western, Flow Cytometry, Immunoprecipitation, Cell Adhesion, Signal Transduction, Cell Movement, Amino Acid Sequence, Protein Binding, Sequence Homology, Amino Acid, Phosphorylation, Molecular Sequence Data, Syndecan-4, Recycling, ADP-Ribosylation Factor 6
Depositing User:	Symplectic Admin
Date Deposited:	18 Nov 2016 09:56
Last Modified:	17 Feb 2023 02:00
DOI:	10.1016/j.devcel.2013.01.027
Open Access URL:	http://www.cell.com/developmental-cell/pdf/S1534-5...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3004580