title: 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 identified the VPS21 gene, encoding a Rab GTPase, as such a suppressor. When the vps21Δ mutation was introduced into a deletion mutant of the SUR4 gene, which encodes a VLCFA elongase, a synthetic growth defect was observed. Endosome-mediated vesicular trafficking pathways, including endocytosis and the carboxypeptidase Y (CPY) pathway, were severely impaired in sur4Δ vps21Δ double mutants, while the AP-3 pathway that bypasses the endosome was unaffected. In addition, the sur4Δ mutant 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 trafficking pathways, requirement of VLCFAs is especially high in the endosomal pathways.
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors: Keisuke
authors: K
authors: Obara
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors: Ryo
authors: R
authors: Kojima
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors: Akio
authors: A
authors: Kihara
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D043402:Cathepsin A / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics
chemical_list: D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; C065531:VPS3 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D000123:Acetyltransferases; C107119:SUR4 protein, S cerevisiae; D043402:Cathepsin A; C086866:VPS21 protein, S cerevisiae; D020691:rab GTP-Binding Proteins