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PMID:20978238
| Citation |
Tian, D, Jacobo, SM, Billing, D, Rozkalne, A, Gage, SD, Anagnostou, T, Pavenstädt, H, Pavenstaedt, H, Hsu, HH, Schlondorff, J, Ramos, A and Greka, A (2010) Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci Signal 3:ra77 |
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| 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 (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. |
| Links |
PubMed PMC3071756 Online version:10.1126/scisignal.2001200 |
| Keywords |
Actins/genetics; Actins/metabolism; Animals; Calcium/metabolism; Calcium Signaling/physiology; Cell Movement/physiology; HEK293 Cells; Humans; Mice; Neuropeptides/genetics; Neuropeptides/metabolism; TRPC Cation Channels/genetics; TRPC Cation Channels/metabolism; rac GTP-Binding Proteins/genetics; rac GTP-Binding Proteins/metabolism; rho GTP-Binding Proteins/genetics; rho GTP-Binding Proteins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0090280: positive regulation of calcium ion import |
ECO:0000315: |
P |
Fig 1. TRPC5- or TRPC6-depleted cells showed a statistically significant reduction in the peak amplitude of the Ca2+ transients as compared to controls. In the presence of shRNA directed against TRPC5 or TRPC6, the Ca2+ response after addition of 2 mM Ca2+ to the bath was significantly diminished by 60 and 50%, respectively. |
complete | ||||
See also
References
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