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PMID: 17485492 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix.

The Journal of cell biology ·Vol. 177 ·No. 3 ·2007-05-07 ·Pages 527-38

Bass MD, Roach KA, Morgan MR, Mostafavi-Pour Z, Schoen T, Muramatsu T, Mayer U, Ballestrem C, Spatz JP, Humphries MJ

Abstract

Cell migration in wound healing and disease is critically dependent on integration with the extracellular matrix, but the receptors that couple matrix topography to migratory behavior remain obscure. Using nano-engineered fibronectin surfaces and cell-derived matrices, we identify syndecan-4 as a key signaling receptor determining directional migration. In wild-type fibroblasts, syndecan-4 mediates the matrix-induced protein kinase Calpha (PKCalpha)-dependent activation of Rac1 and localizes Rac1 activity and membrane protrusion to the leading edge of the cell, resulting in persistent migration. In contrast, syndecan-4-null fibroblasts migrate randomly as a result of high delocalized Rac1 activity, whereas cells expressing a syndecan-4 cytodomain mutant deficient in PKCalpha regulation fail to localize active Rac1 to points of matrix engagement and consequently fail to recognize and respond to topographical changes in the matrix.

MeSH Terms
Animals Cell Movement/genetics Cells, Cultured Enzyme Activation/genetics Extracellular Matrix Fibroblasts/cytology,metabolism Fibronectins Mice Mice, Knockout Mutation Neuropeptides/genetics,metabolism Protein Kinase C-alpha/deficiency,metabolism Protein Structure, Tertiary/genetics Syndecan-4/genetics,metabolism rac GTP-Binding Proteins/genetics,metabolism rac1 GTP-Binding Protein
Chemicals
Fibronectins Neuropeptides Rac1 protein, mouse Sdc4 protein, mouse Syndecan-4 Protein Kinase C-alpha rac GTP-Binding Proteins rac1 GTP-Binding Protein
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Bass Mark D
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, England, UK.
Roach Kirsty A
Morgan Mark R
Mostafavi-Pour Zohreh
Schoen Tobias
Muramatsu Takashi
Mayer Ulrike
Ballestrem Christoph
Spatz Joachim P
Humphries Martin J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200610076
Published
2007-05-07
Pages
527-38
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC1885470
Subset
IM
Grants
Wellcome Trust · 045225 · United Kingdom
Wellcome Trust · 074941 · United Kingdom
Wellcome Trust · 077100 · United Kingdom
Wellcome Trust · United Kingdom
Wellcome Trust · 061149 · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200610076 PMC Full Text View journal details
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