Canonical transient receptor potential (TRPC) 1 acts as a negative regulator for vanilloid TRPV6-mediated Ca2+ influx

J Biol Chem. 2012 Oct 12;287(42):35612-20. doi: 10.1074/jbc.M112.400952. Epub 2012 Aug 29.


TRP proteins mostly assemble to homomeric channels but can also heteromerize, preferentially within their subfamilies. The TRPC1 protein is the most versatile member and forms various TRPC channel combinations but also unique channels with the distantly related TRPP2 and TRPV4. We show here a novel cross-family interaction between TRPC1 and TRPV6, a Ca(2+) selective member of the vanilloid TRP subfamily. TRPV6 exhibited substantial co-localization and in vivo interaction with TRPC1 in HEK293 cells, however, no interaction was observed with TRPC3, TRPC4, or TRPC5. Ca(2+) and Na(+) currents of TRPV6-overexpressing HEK293 cells are significantly reduced by co-expression of TRPC1, correlating with a dramatically suppressed plasma membrane targeting of TRPV6. In line with their intracellular retention, remaining currents of TRPC1 and TRPV6 co-expression resemble in current-voltage relationship that of TRPV6. Studying the N-terminal ankyrin like repeat domain, structurally similar in the two proteins, we have found that these cytosolic segments were sufficient to mediate a direct heteromeric interaction. Moreover, the inhibitory role of TRPC1 on TRPV6 influx was also maintained by expression of only its N-terminal ankyrin-like repeat domain. Our experiments provide evidence for a functional interaction of TRPC1 with TRPV6 that negatively regulates Ca(2+) influx in HEK293 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ankyrin Repeat
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • HEK293 Cells
  • Humans
  • Ion Channel Gating / physiology*
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*


  • Calcium Channels
  • TRPC Cation Channels
  • TRPV Cation Channels
  • TRPV6 protein, human
  • transient receptor potential cation channel, subfamily C, member 1
  • Calcium