Tricalbins are required for nonvesicular ceramide transport at ER-Golgi contacts and modulate lipid droplet biogenesis

SUMMARY Lipid composition varies among organelles and the distinct lipid composition is important for specific functions of each membrane. Lipid transport between organelles, which is critical for the maintenance of membrane lipid composition, occurs by either vesicular or nonvesicular mechanisms. In yeast, ceramide synthesized in the endoplasmic reticulum (ER) is transported to the Golgi apparatus where inositolphosphorylceramide (IPC) is formed. Here we show that a fraction of Tcb3p, a yeast tricalbin protein localizes to ER-Golgi contact sites. Tcb3p and their homologs Tcb1p and Tcb2p are required for formation of ER-Golgi contacts and nonvesicular ceramide transport. Absence of Tcb1p, Tcb2p and Tcb3p increases acylceramide synthesis and subsequent lipid droplet (LD) formation. As LD can sequester excess lipids, we propose that tricalbins act as regulators of ceramide transport at ER-Golgi contact sites to help reduce a potentially toxic accumulation of ceramides.