Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix |
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| Authors: | Bass Mark D 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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| Affiliation: | Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, England, UK. |
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| 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. |
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