Retinal phospholipase C from squid is a regulator of Gq alpha GTPase activity

The phospholipase C (PLC) pathway is the major signaling mechanism of photo activation in invertebrate photoreceptors. Here we report the cloning of a cDNA encoding a 140-kDa retinal PLC that is uniquely expressed in squid pho toreceptors. This cDNA encodes a protein with multiple distinct modular dom ains: PH, X and Y catalytic, and C2 domains, as well as G- and P-box motifs and two GTP/ATP binding motifs. The PLC was stimulated by activated squid Gq alpha but not by squid Gq beta gamma or mammalian beta gamma subunits. T he PLC was inhibited by monophosphate, diphosphate and triphosphate nucleot ides but not cyclic nucleosides. We also tested the ability of PLC-140 to r egulate the GTPase activity of Gq alpha. in the rhabdomeric membranes. Depl etion of PLC-140 from the rhabdomeric membranes decreased the GTP hydrolysi s but not GTP-gammaS binding to the membranes. Reconstitution of purified P LC-140 with membranes accelerated Gq alpha GTPase activity by fivefold at a concentration of 2.5 mum. Our data suggest that PLC-140 plays an important role in both the activation and inactivation pathways of invertebrate visu al transduction.