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Sci. Signal., 26 October 2010
Vol. 3, Issue 145, p. ra77
[DOI: 10.1126/scisignal.2001200]

RESEARCH ARTICLES

Antagonistic Regulation of Actin Dynamics and Cell Motility by TRPC5 and TRPC6 Channels

Dequan Tian1*, Sarah M. P. Jacobo1*, David Billing1, Anete Rozkalne1, Steven D. Gage1, Theodora Anagnostou1, Hermann Pavenstädt2, Hsiang-Hao Hsu3, Johannes Schlondorff4, Arnolt Ramos1, and Anna Greka1{dagger}

1 Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.
2 Medizinische Klinik und Poliklinik D, 48149 Muenster, Germany.
3 Chang Gung Memorial Hospital and University, Taoyuan 333, Taiwan.
4 Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.

* These authors contributed equally to this work.

Abstract: 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 Ca2+ 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.

{dagger} To whom correspondence should be addressed. E-mail: greka.anna{at}mgh.harvard.edu

Citation: D. Tian, S. M. P. Jacobo, D. Billing, A. Rozkalne, S. D. Gage, T. Anagnostou, H. Pavenstädt, H.-H. Hsu, J. Schlondorff, A. Ramos, A. Greka, Antagonistic Regulation of Actin Dynamics and Cell Motility by TRPC5 and TRPC6 Channels. Sci. Signal. 3, ra77 (2010).

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