Research ArticleCell Migration

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

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Science Signaling  26 Oct 2010:
Vol. 3, Issue 145, pp. ra77
DOI: 10.1126/scisignal.2001200

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Signaling Stop and Go

Calcium-dependent remodeling of the actin cytoskeleton through members of the Rho family of small guanosine triphosphatases (Rho GTPases) is crucial for cell migration. Tian et al. investigated the upstream regulation of this process in kidney podocytes, a class of cells associated with glomerular capillaries whose contractile function is crucial to maintenance of the kidney filtration barrier. They found that, although angiotensin II elicited calcium influx through both TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels, TRPC5 signaled through Rac1 to promote cell motility, whereas TRPC6 signaled through RhoA to inhibit it. Mechanistic analyses indicated that differential activation of the two GTPases depended on their location relative to the two channels: TRPC5 was present in a complex with Rac1 and TRPC6 was associated with RhoA, enabling their antagonistic regulation of the cytoskeleton and thereby their opposing effects on cell migration.

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