Characterization of Caenorhabditis elegans sphingomyelin synthases through heterologous expression

Abstract

Sphingomyelin (SM) is a major component of mammalian cell membranes and is particularly abundant in the myelin sheath that surrounds nerve fibers. Its production is catalyzed by SM synthases, SMS1 and SMS2, which interconvert phosphatidylcholine and ceramide into diacylglycerol and SM, respectively, in the Golgi and at the plasma membrane. As the lipids participating in this reaction fulfill both structural and signaling functions, SMS enzymes have considerable potential to influence diverse important cellular processes. The nematode Caenorhabditis elegans is an attractive model for studying both animal development and human disease. The organism contains five SMS homologues, but none of these have been characterized in any detail. Here, we carried out the first systematic analysis of SMS family members in C. elegans. Using heterologous expression systems, genetic ablation, metabolic labeling, and lipidome analyses, we show that C. elegans harbors at least three distinct SM synthases and one ceramide phosphoethanolamine (CPE) synthase. Moreover, C. elegans SMS family members have partially overlapping but also unique subcellular distributions, and together they occupy all principal compartments of the secretory pathway. Our findings shed light on crucial aspects of sphingolipid metabolism in a valuable animal model and open avenues for exploring the role of SM and its metabolic intermediates in organismal development.