The closing and opening of TRPC channels by Homer1 and STIM1

Influx of Ca2+ is a central component of the receptor-evoked Ca2+ signal. A ubiquitous form of Ca2+ influx comes from Ca2+ channels that are activated in response to depletion of the endoplasmic reticulum Ca2+ stores and are thus named the store-operated Ca2+-influx channels (SOCs). One form of SOC is the transient receptor potential canonical (TRPC) channels. A major question in the field of Ca2+ 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 IP3 receptors (IP3Rs) to keep these channels in the closed state. Dissociation of the TRPCs-Homer-IP3Rs complex allows STIM1 access to the TRPC channels negative charges to gate open these channels.