Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors.
Receptor signaling at the plasma membrane often releases calcium from intracellular stores. For example, inositol triphosphate (IP3) produced by receptor-coupled phospholipase C activates an intracellular store calcium channel, the IP(3)R. Conversely, stores can induce extracellular calcium to enter the cell through plasma membrane channels, too. How this "reverse" coupling works was unclear, but store IP(3)Rs were proposed to bind and regulate plasma membrane TRP cation channels. Here, we demonstrate that the adaptor protein, termed Homer, facilitates a physical association between TRPC1 and the IP(3)R that is required for the TRP channel to respond to signals. The TRPC1-Homer-IP(3)R complex is dynamic and its disassembly parallels TRPC1 channel activation. Homer's action depends on its ability to crosslink and is blocked by the dominant-negative immediate early gene form, H1a. Since H1a is transcriptionally regulated by cellular activity, this mechanism can affect both short and long-term regulation of TRPC1 function.
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating / Q000502:physiology*; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D050052:TRPC Cation Channels
D015220:Calcium Channels; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046911:Macromolecular Substances; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium