Involvement of Rab9 and Rab11 in the intracellular trafficking of TRPC6

Biochim Biophys Acta. 2010 Jul;1803(7):805-12. doi: 10.1016/j.bbamcr.2010.03.010. Epub 2010 Mar 24.


TRPC proteins become involved in Ca2+ entry following the activation of Gq-protein coupled receptors. TRPC6 is inserted into the plasma membrane upon stimulation and remains in the plasma membrane as long as the stimulus is present. However, the mechanism that regulates the trafficking of TRPC6 is unclear. In the present study, we highlighted the involvement of two Rab GTPases in the trafficking of TRPC6. Rab9 co-localized in vesicular structures with TRPC6 in HeLa cells and co-immunoprecipitated with TRPC6. When co-expressed with TRPC6, Rab9(S21N), a dominant negative mutant, caused an increase in the level of TRPC6 at the plasma membrane and in TRPC6-mediated Ca2+ entry upon activation by a muscarinic receptor agonist. Similarly, the expression of Rab11 also caused an increase in TRPC6 expression at the cell surface and an increase in TRPC6-mediated Ca2+ entry. The co-expression of TRPC6 with the dominant negative mutant Rab11(S25N) abolished CCh-induced TRPC6 activation and reduced the level of TRPC6 at the plasma membrane. This study demonstrates that the trans-Golgi network and recycling endosomes are involved in the intracellular trafficking of TRPC6 by regulating channel density at the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Cell Membrane / metabolism
  • HeLa Cells
  • Humans
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPC6 Cation Channel
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*


  • Recombinant Fusion Proteins
  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • RAB9A protein, human
  • rab11 protein
  • rab GTP-Binding Proteins