[Receptor-activated Ca2+ influx: capacitative Ca2+ entry and TRP proteins].
Receptor-activated Ca2+ channels (RACC) are triggered in response to activation of G protein-coupled receptors or tyrosine kinase-coupled receptors. RACCs, together with voltage-dependent Ca2+ channels, form physiologically the most important Ca2+ influx pathways, being highly diverged in activation mechanisms and Ca2+ permeability. Characterization of mammalian homologues of Drosophila TRP proteins has been an important clue for understanding molecular mechanisms underlying receptor-activated Ca2+ influx in vertebrate cells. Recent issues have been whether any members of the TRP family form capacitative Ca2+ entry (CCE) channels activated by release of Ca2+ from internal stores and their depletion. We have isolated cDNAs that encode seven mouse TRP homologues, TRP1-7. TRP homologues are distributed differently among tissues, although they are all abundant in the brain. Functional characterization of TRP proteins recombinantly expressed in HEK cells indicate that TRP5 is highly permeable to Ca2+, while TRP3 and 7 are non-selective cation channels. The results demonstrate that TRP3,5,7 are capable of generating Ca2+ currents after desensitization of the stimulated G-protein-coupled receptors and replenishment of stores, suggesting that store depletion is not necessary to maintain activity of the TRP homologues. Ca2+ positively regulates TRP channels through Ca(2+)-calmodulin pathways, but via different Ca(2+)-calmodulin-dependent enzymes. Thus, activation of TRP channels is not tightly coupled with store depletion as CCE, suggesting that CCE (or CRAC) channels are molecular entities separate from TRP.
Mori
Y
Y
Department of Information Physiology, National Institute for Physiological Sciences, Aichi, Japan.
Okada
T
T
Shimizu
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D050052:TRPC Cation Channels
D015220:Calcium Channels; D011956:Receptors, Cell Surface; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D002118:Calcium