title: The closing and opening of TRPC channels by Homer1 and STIM1.
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(3) Rs) to keep these channels in the closed state. Dissociation of the TRPCs-Homer-IP(3) Rs complex allows STIM1 access to the TRPC channels negative charges to gate open these channels.
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Yuan
authors.forename: K P
authors.initials: KP
authors.lastname: Lee
authors.forename: J H
authors.initials: JH
authors.lastname: Hong
authors.forename: S
authors.initials: S
authors.lastname: Muallem
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology; D000072233:Homer Scaffolding Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000378:metabolism* / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; D002118:Calcium