| First Author | Heck JN | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 13 | Pages | 2583-92 |
| PubMed ID | 22593214 | Mgi Jnum | J:198765 |
| Mgi Id | MGI:5499090 | Doi | 10.1091/mbc.E11-10-0876 |
| Citation | Heck JN, et al. (2012) Microtubules regulate GEF-H1 in response to extracellular matrix stiffness. Mol Biol Cell 23(13):2583-92 |
| abstractText | Breast epithelial cells sense the stiffness of the extracellular matrix through Rho-mediated contractility. In turn, matrix stiffness regulates RhoA activity. However, the upstream signaling mechanisms are poorly defined. Here we demonstrate that the Rho exchange factor GEF-H1 mediates RhoA activation in response to extracellular matrix stiffness. We demonstrate the novel finding that microtubule stability is diminished by a stiff three-dimensional (3D) extracellular matrix, which leads to the activation of GEF-H1. Surprisingly, activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway did not contribute to stiffness-induced GEF-H1 activation. Loss of GEF-H1 decreases cell contraction of and invasion through 3D matrices. These data support a model in which matrix stiffness regulates RhoA through microtubule destabilization and the subsequent release and activation of GEF-H1. |
