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

SERGEJ LIMAR; CAROLIN KÖRNER; FERNANDO MARTÍNEZ-MONTAÑÉS; VIKTORIYA G. STANCHEVA; VERENA N. WOLF; STEFAN WALTER; ELIZABETH A. MILLER; CHRISTER S. EJSING; GALASSI, VANESA VIVIANA; FLORIAN FRÖHLICH

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Lugar: New York; Año: 2023 vol. 222

0021-9525

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). Ceramides have to be transported between the ER and the Golgi. In mammalian cells, this task is executed by the ceramide transport protein (CERT). However, yeast cells lack a CERT homolog and the mechanism of ER to Golgi ceramide transport remains largely elusive. Here, we identify yeast Svf1 functioning in ceramide transport between the ER and the Golgi. Svf1 is targetedto membranes via an N-terminal amphipathic helix (AH). Svf1 binds ceramide in a hydrophobic binding pocket that is located in between two lipocalin domains. We show that Svf1 membrane-targeting is important to maintain flux of ceramides into complex SPs. Together, our results suggest that Svf1 is a ceramide binding protein that transports ceramides between the endoplasmic reticulum and the cis-Golgi apparatus in yeast.