Ceramide transfer protein regulates G-protein coupled phospholipase signalling in Drosophila photoreceptors.

Abstract

The non-vesicular transfer of lipids between organelles at membrane contact sites (MCS) has been proposed as a key principle in the regulation of cell physiology. While several proteins with lipid transfer activity have been identified and localized to MCS, their functional significance for supporting physiology is poorly understood. Ceramide transfer protein (CERT) is one such molecule that can transfer ceramide between membranes in vitro. However, evidence for the mechanism and in vivo significance of CERT function is limited. In this study, we have analyzed the function of the only gene (dcert) encoding CERT in Drosophila. We find that loss of function alleles of dcert (dcert1), show elevated levels of short chain ceramide species along with a reduction in the levels of its metabolite phosphatidyl ethanolamine ceramide. Physiological analysis of dcert1 mutant alleles showed reduced electrical responses in the eye to light stimulation although photoreceptors did not undergo retinal degeneration, and this phenotype could be rescued by reconstitution of dcert1 with the wild type gene. The altered light response in dcert1 was associated with a reduction in the rate of phosphatidylinositol 4,5 bisphosphate (PIP2) resynthesis following light induced phospholipase C (PLC) stimulation. The reduced electrical response of dcert1 could be suppressed by reducing ceramide synthesis at the ER. Taken together, our findings suggest that ceramide synthesized at the ER and transferred to the Golgi by CERT regulates G-protein coupled phospholipase C signaling in vivo.