The closing and opening of TRPC channels by Homer1 and STIM1

J. P. Yuan, K. P. Lee, J. H. Hong, S. Muallem

Research output: Contribution to journalReview article

49 Scopus citations

Abstract

Influx of Ca 2+ is a central component of the receptor-evoked Ca 2+ signal. A ubiquitous form of Ca 2+ influx comes from Ca 2+ channels that are activated in response to depletion of the endoplasmic reticulum Ca 2+ stores and are thus named the store-operated Ca 2+-influx channels (SOCs). One form of SOC is the transient receptor potential canonical (TRPC) channels. A major question in the field of Ca 2+ signalling is the molecular mechanism that regulates the opening and closing of these channels. All TRPC channels have a Homer-binding ligand and two conserved negative charges that interact with two terminal lysines of the stromal interacting molecule 1 (STIM1). The Homer and STIM1 sites are separated by only four amino acid residues. Based on available results, we propose a molecular mechanism by which Homer couples TRPC channels to IP 3 receptors (IP 3Rs) to keep these channels in the closed state. Dissociation of the TRPCs-Homer-IP 3Rs complex allows STIM1 access to the TRPC channels negative charges to gate open these channels.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalActa Physiologica
Volume204
Issue number2
DOIs
StatePublished - 1 Feb 2012

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Keywords

  • Ca influx
  • Homer1
  • STIM1

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