First Author | Bass MD | Year | 2007 |
Journal | J Cell Biol | Volume | 177 |
Issue | 3 | Pages | 527-38 |
PubMed ID | 17485492 | Mgi Jnum | J:134723 |
Mgi Id | MGI:3789567 | Doi | 10.1083/jcb.200610076 |
Citation | Bass MD, et al. (2007) Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix. J Cell Biol 177(3):527-38 |
abstractText | 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. |