Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking.

ABSTRACT: The complex sphingolipids exhibit a diversity of ceramide acyl chain structures that influence their trafficking and intracellular distributions, but it remains unclear how the cell discerns among the different ceramides to affect such sorting. To address the mechanism, we synthesize a library of GM1 glycosphingolipids with naturally varied acyl chains and quantitatively assess their sorting among different endocytic pathways. We find that a stretch of at least 14 saturated carbons extending from C1 at the water-bilayer interface dictate lysosomal sorting by exclusion from endosome sorting tubules. Sorting to the lysosome by the C14^∗ motif is cholesterol dependent. Perturbations of the C14^∗ motif by unsaturation enable GM1 entry into endosomal sorting tubules of the r

SUBMITTER: Schmieder SS 

PROVIDER: S-EPMC9358721 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature