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Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels

Dequan Tian1, Sarah M P Jacobo, David Billing

  • 1Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.

Science Signaling
|October 28, 2010
PubMed

Insights

Transient receptor potential (TRPC) channels TRPC5 and TRPC6 oppositely regulate cell migration by controlling calcium ion influx and Rho GTPase activity. TRPC5 promotes migration via Rac1, while TRPC6 inhibits it via RhoA.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Rho GTPases (RhoA, Cdc42, Rac1) are key regulators of cell migration.
  • Calcium ion (Ca(2+)) microdomains are crucial for localized Rho GTPase activity and cell motility.
  • Understanding the upstream regulators of Rho GTPase signaling in cell migration is essential.

Purpose of the Study:

  • To identify and characterize the role of ion channels in regulating Rho GTPase activity and cell migration.
  • To elucidate the specific TRPC channels involved in controlling actin remodeling and cell motility.
  • To investigate the molecular complexes formed by TRPC channels and Rho GTPases.

Main Methods:

  • Identification of TRPC5 and TRPC6 channels in fibroblasts and kidney podocytes.
  • Co-immunoprecipitation assays to determine molecular complexes between TRPC channels and Rho GTPases.
  • Measurement of Ca(2+) influx and Rho GTPase activation (Rac1 and RhoA).
  • Assessment of cell migration and actin remodeling in response to TRPC channel activity.

Main Results:

  • TRPC5 channels form a complex with Rac1, and their activation promotes cell migration through Ca(2+) influx.
  • TRPC6 channels form a complex with RhoA, and their activation inhibits cell migration via Ca(2+) influx.
  • TRPC5 and TRPC6 act antagonistically to regulate actin remodeling and cell motility.
  • TRPC5-mediated Ca(2+) influx activates Rac1, while TRPC6-mediated Ca(2+) influx activates RhoA.

Conclusions:

  • Receptor-activated TRPC5 and TRPC6 channels are identified as antagonistic regulators of cell migration.
  • TRPC5 and TRPC6 mediate distinct Ca(2+) influx pathways that differentially regulate Rac1 and RhoA.
  • Antagonistic Ca(2+) influx pathways represent a conserved mechanism for integrated regulation of cell migration.

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