TY - JOUR
T1 - Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels
AU - Tian, Dequan
AU - Jacobo, Sarah M.P.
AU - Billing, David
AU - Rozkalne, Anete
AU - Gage, Steven D.
AU - Anagnostou, Theodora
AU - Pavenstaedt, Hermann
AU - Hsu, Hsiang Hao
AU - Schlondorff, Johannes
AU - Ramos, Arnolt
AU - Greka, Anna
PY - 2010/10/26
Y1 - 2010/10/26
N2 - 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 (Ca2+) 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 Ca2+ influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca2+ influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration.
AB - 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 (Ca2+) 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 Ca2+ influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca2+ influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration.
UR - http://www.scopus.com/inward/record.url?scp=78049524253&partnerID=8YFLogxK
U2 - 10.1126/scisignal.2001200
DO - 10.1126/scisignal.2001200
M3 - 文章
C2 - 20978238
AN - SCOPUS:78049524253
SN - 1945-0877
VL - 3
JO - Science Signaling
JF - Science Signaling
IS - 145
M1 - ra77
ER -