Multiple roles of calmodulin and other Ca(2+)-binding proteins in the functional regulation of TRP channels.
Transient receptor potential channels (TRP) have emerged as cellular sensors of various internal and external cues. Generally, the activation of TRP canonical (TRPC) channels is triggered by the stimulation of phospholipase C; however, multiple factors are involved in the regulation of these channels. Among them, Ca(2+)-mediated feedback channel modulations are often mediated by calmodulin (CaM) and other Ca(2+)-binding proteins. In vitro binding studies have revealed multiple CaM-binding sites on TRPC proteins. Among them, a common CaM/inositol 1,4,5-trisphosphate receptor-binding site is found at the carboxyl terminus of every TRPC isoform. Additional non-conserved CaM-binding sites are present at the amino and carboxyl termini of several TRPC proteins. Likewise, multiple CaM-binding sites were found in other TRP proteins. These, together with the presence in close vicinity of the interaction sites for the related neuronal Ca(2+)-binding proteins, such as CaBP1, suggest a multitude of diverse intracellular Ca(2+)-dependent regulations of TRP channels. Functional studies have begun to reveal the unique roles of CaM and CaBP1 binding to several TRP channels. This review will focus on the CaM- and CaBP1-mediated regulations of TRPC channels. Related studies on TRPM and TRPV channels will also be highlighted.
Zhu
Michael Xi
MX
Department of Neuroscience and the Center for Molecular Neurobiology, The Ohio State University, 168 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210, USA. zhu.55@osu.edu
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015220:Calcium Channels / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D016415:Sequence Alignment; D050052:TRPC Cation Channels / Q000502:physiology*; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002147:Calmodulin; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C085577:Ca2+-binding protein-1