Structure, function, and control of phosphoinositide-specific phospholipase C

Phosphoinositide-specific phospholipase C (PLC) subtypes beta, gamma, and d elta comprise a related group of multidomain phosphodiesterases that cleave the polar head groups from inositol lipids. Activated by all classes of ce ll surface receptor, these enzymes generate the ubiquitous second messenger s inositol 1,4,5-trisphosphate and diacylglycerol. The last 5 years have se en remarkable advances in our understanding of the molecular and biological facets of PLCs. New insights into their multidomain arrangement and cataly tic mechanism have been gained from crystallographic studies of PLC-delta(1 ), while new modes of controlling PLC activity have been uncovered in cellu lar studies. Most notable is the realization that PLC-beta, -gamma, and -de lta isoforms act in concert, each contributing to a specific aspect of the cellular response. Clues to their true biological roles were also obtained. Long assumed to function broadly in calcium-regulated processes, genetic s tudies in yeast, slime molds, plants, flies, and mammals point to specific and conditional roles for each PLC isoform in cell signaling and developmen t. In this review we consider each subtype of PLC in organisms ranging from yeast to mammals and discuss their molecular regulation and biological fun ction.