Ceramide transfer protein regulates G-protein–coupled phospholipase signalling in photoreceptors

Non-vesicular lipid transfer at membrane contact sites (MCS) is proposed as a key principle in eukaryotic cells. While several lipid transfer proteins (LTPs) are localized at MCS, their physiological significance is poorly understood. Ceramide transfer protein (CERT) transfers ceramide between membranes in vitro. However, evidence for the in vivo significance of CERT function is limited. We find that loss of dcert, the only gene encoding CERT in Drosophila, results in elevated levels of short-chain ceramides along with reductions in the levels of its metabolite phosphoethanolamine ceramide in photoreceptors. Physiological analysis showed a reduced electrical response to light stimulation in dcert mutants. dcert mutants showed a reduction in the rate of phosphatidylinositol 4,5-bisphosphate (PIP₂) resynthesis following light-induced phospholipase C (PLC) stimulation, associated with reduced ER-plasma membrane MCS density and function of the MCS-localized protein RDGB. Together, our findings suggest that CERT function regulates G-protein–coupled PLC signalling through modulation of MCS function in vivo.