Effects on vesicular transport pathways at the late endosome in cells with limited very long-chain fatty acids

Abstract

Very long-chain fatty acids (VLCFAs), fatty acids with chain-length greater than 20 carbons , possess a wide range of biological functions. However, their roles at the molecular level remain largely unknown. In the present study, we screened for multicopy suppressors that rescued temperature-sensitive growth of VLCFA-limited yeast cells, and we identifi ed the VPS21 gene, encoding a Rab GTPase, as such a suppressor. When the vps21mutation was introduced into a deletion mutant of the SUR4 gene, which encodes a VLCFA elongase, a synthetic growth defect was observed. Endosome-mediated vesicular traffi cking pathways, including endocytosis and the carboxypeptidase Y (CPY) pathway, were severely impaired in sur4vps21double mutants, while the AP-3 pathway that bypasses the endosome was unaffected. In addition, the sur4mutant also exhibited a synthetic growth defect when combined with the deletion of VPS3 , which encodes a subunit of the class C core vacuole/endosome tethering (CORVET) complex that tethers transport vesicles to the late endosome/multivesicular body (MVB). These results suggest that, of all the intracellular traffi cking pathways, requirement of VLCFAs is especially high in the endosomal pathways.Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc..