RDGBα, a PI-PA transfer protein regulates G-protein coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction

Abstract

Many membrane receptors activate phospholipase C (PLC) during signalling, triggering changes in the levels of several plasma membrane (PM) lipids including PtdIns, PtdOH and PtdIns(4,5)P2. It is widely believed that exchange of lipids between the PM and endoplasmic reticulum (ER) is required to restore lipid homeostasis during PLC signalling, yet the mechanism remains unresolved. RDGB is a multi-domain protein with a PITP domain (RDGB-PITPd). We find that in vitro, RDGB-PITPd binds and transfers both PtdOH and PtdIns. In Drosophila photoreceptors that experience high rates of PLC activity, RDGB function is essential for phototransduction. We show that binding of PtdIns to RDGB-PITPd is essential for normal phototransduction; yet this property is insufficient to explain in vivo function since another Drosophila PITP (vib) that also binds PtdIns cannot rescue the phenotypes of RDGB deletion. In RDGB mutants, PtdIns(4,5)P2 resynthesis at the PM following PLC activation is delayed and PtdOH levels elevate. Thus RDGB couples the turnover of both PtdIns and PtdOH, key lipid intermediates during G-protein coupled PtdIns(4,5)P2 turnover.