| First Author | King SJ | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 9 | Pages | 1705-18 |
| PubMed ID | 21427700 | Mgi Jnum | J:172000 |
| Mgi Id | MGI:5002755 | Doi | 10.1038/emboj.2011.82 |
| Citation | King SJ, et al. (2011) beta1 integrins regulate fibroblast chemotaxis through control of N-WASP stability. EMBO J 30(9):1705-18 |
| abstractText | Chemotactic migration of fibroblasts towards growth factors, such as during development and wound healing, requires precise spatial coordination of receptor signalling. However, the mechanisms regulating this remain poorly understood. Here, we demonstrate that beta1 integrins are required both for fibroblast chemotaxis towards platelet-derived growth factor (PDGF) and growth factor-induced dorsal ruffling. Mechanistically, we show that beta1 integrin stabilises and spatially regulates the actin nucleating endocytic protein neuronal Wiskott-Aldrich syndrome protein (N-WASP) to facilitate PDGF receptor traffic and directed motility. Furthermore, we show that in intact cells, PDGF binding leads to rapid activation of beta1 integrin within newly assembled actin-rich membrane ruffles. Active beta1 in turn controls assembly of N-WASP complexes with both Cdc42 and WASP-interacting protein (WIP), the latter of which acts to stabilise the N-WASP. Both of these protein complexes are required for PDGF internalisation and fibroblast chemotaxis downstream of beta1 integrins. This represents a novel mechanism by which integrins cooperate with growth factor receptors to promote localised signalling and directed cell motility. |
