First Author | Tian D | Year | 2010 |
Journal | Sci Signal | Volume | 3 |
Issue | 145 | Pages | ra77 |
PubMed ID | 20978238 | Mgi Jnum | J:259315 |
Mgi Id | MGI:6142197 | Doi | 10.1126/scisignal.2001200 |
Citation | Tian D, et al. (2010) Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci Signal 3(145):ra77 |
abstractText | The Rho family of small guanosine triphosphatases (Rho GTPases: RhoA, Cdc42, and Rac1) regulates many aspects of cell behavior, including actin dynamics and cell migration. The generation of calcium ion (Ca(2+)) microdomains is critical in promoting cell migration because they control the localized activity of Rho GTPases. We identified receptor-activated TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels as antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes. We show that TRPC5 is in a molecular complex with Rac1, whereas TRPC6 is in a molecular complex with RhoA. TRPC5-mediated Ca(2+) influx induces Rac1 activation, thereby promoting cell migration, whereas TRPC6-mediated Ca(2+) influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca(2+) influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration. |