Assembly and gating of TRPC channels in signalling microdomains.
A variety of plasmalemmal Ca2+-permeable channels, many of which are assembled from TRPC channels and are regulated by elements of the phosphatidylinositol pathway, may fulfil the role of store-operated channels (SOCs) and receptor-operated channels (ROCs). Growing evidence suggests that TRPC channels are clustered into spatially restricted microdomains that are important interaction sites for signalling molecules and for the induction of selective cellular responses. For example, TRPC1, which is activated solely by the depletion of internal stores in neurons, is assembled in a Ca2+ signalling complex, composed of the bradykinin receptor, G alpha(q) subunit, phospholipase C (PLC)beta and inositol 1,4,5-trisphosphate receptor (IP3R) whereas TRPC6, which is activated by phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis per se, is evenly distributed. Thus, differential targeting of TRPCs in microdomains allows different receptors to selectively recruit different Ca2+ entry pathways. TRPCs also co-assemble with members of the TRPP group, the polycystins. Because the polycystin proteins are thought to function as sensors of the extracellular environment, it can be hypothesized that TRPC channels are involved in a wide range of cellular functions other than those of SOCs and ROCs, including mechanotransduction.
Delmas
Patrick
P
Intégration des Informations Sensorielles, CNRS, UMR 6150, IFR Jean Roche, Faculté de Médecine, Bd. Pierre Dramard, 13916 Marseille, France.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D004594:Electrophysiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D054799:Phospholipase C beta; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D050052:TRPC Cation Channels; D050396:TRPP Cation Channels; D010738:Type C Phospholipases / Q000378:metabolism
D002118:Calcium; D015220:Calcium Channels; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels; D007527:Isoenzymes; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D054799:Phospholipase C beta; D011506:Proteins; D018002:Receptors, Bradykinin; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; D050396:TRPP Cation Channels; D010738:Type C Phospholipases; C104603:TRPC3 cation channel; C492145:Trpc6 protein, rat; C096351:transient receptor potential cation channel, subfamily C, member 1