Inositol lipids and TRPC channel activation.
The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or 'gates'. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1-TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.
Putney
James W
JW
National Institute of Environmental Health Sciences, NIH, Department of Health and Human Services, Research Triangle Park, NC 27709 USA. putney@niehs.nih.gov
D000818:Animals; D004075:Diglycerides / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D050052:TRPC Cation Channels; D010738:Type C Phospholipases