Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface

Abstract

Limar et al. show that the yeast protein Svf1 localizes to the cis Golgi apparatus via an N-terminal amphipathic helix. Svf1 directly binds ceramides and is necessary to maintain appropriate levels of complex sphingolipids, most likely by transporting ceramides between the ER and the Golgi apparatus. Ceramides are essential precursors of complex sphingolipids and act as potent signaling molecules. Ceramides are synthesized in the endoplasmic reticulum (ER) and receive their head-groups in the Golgi apparatus, yielding complex sphingolipids (SPs). Transport of ceramides between the ER and the Golgi is executed by the essential ceramide transport protein (CERT) in mammalian cells. However, yeast cells lack a CERT homolog, and the mechanism of ER to Golgi ceramide transport remains largely elusive. Here, we identified a role for yeast Svf1 in ceramide transport between the ER and the Golgi. Svf1 is dynamically targeted to membranes via an N-terminal amphipathic helix (AH). Svf1 binds ceramide via a hydrophobic binding pocket that is located in between two lipocalin domains. We showed that Svf1 membrane-targeting is important to maintain flux of ceramides into complex SPs. Together, our results show that Svf1 is a ceramide binding protein that contributes to sphingolipid metabolism at Golgi compartments.