STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: moving TRPC1 in and out of lipid rafts

Cell Calcium. 2008 Nov;44(5):479-91. doi: 10.1016/j.ceca.2008.03.001. Epub 2008 May 23.


While the role of members from the TRPC family of channels as receptor-operated channels (ROC) is well established and supported by numerous studies, the role of this family of channels as store-operated channels (SOC) has been the focus of a heated controversy over the last few years. In the present study, we have explored the modulation of STIM1 on human TRPC1 channel. We show that the association of STIM1 to TRPC1 favors the insertion of TRPC1 into lipid rafts, where TRPC1 functions as a SOC. In the absence of STIM1, TRPC1 associates to other members from the TRPC family of channels to form ROCs. A novel TIRFM-FRET method illustrates the relevance of the dynamic association between STIM1 and TRPC1 for the activation of SOC and the lipid raft localization of the STIM1-TRPC1 complex. This study provides new evidence about the dual activity of TRPC1 (forming ROC or SOC) and the partners needed to determine TRPC1 functional fate. It highlights also the role of plasma membrane microdomains and ER-PM junctions in modulating TRPC1 channel function and its association to STIM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Enzyme Inhibitors / metabolism
  • Humans
  • Membrane Microdomains / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Patch-Clamp Techniques
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • Thapsigargin / metabolism


  • Enzyme Inhibitors
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1
  • Thapsigargin