A lipid-mediated quality control process in the Golgi apparatus in yeast.
When heme biosynthesis is disrupted, the yeast Saccharomyces cerevisiae becomes unable to synthesize its major sterol, ergosterol, and desaturate fatty acids. We took advantage of this physiological peculiarity to evaluate the consequences of ergosterol and/or unsaturated fatty acid (UFA) depletions on the biogenesis of a model polytopic plasma membrane protein, the uracil permease Fur4p. We show that under UFA shortage, which results in low amounts of diunsaturated phospholipid species, and under ergosterol depletion, Fur4p is prematurely routed from the Golgi apparatus to the vacuolar lumen in a process that requires the ubiquitin ligase Rsp5p. Interestingly, this diversion is not correlated to Fur4p exclusion from detergent-resistant membranes. In an independent set of experiments, we show that Fur4p targeting to the plasma membrane depends on phosphatidylethanolamine amounts and more specifically on the propensity of this phospholipid to form a hexagonal phase. In light of recent literature, we propose a model in which ergosterol and diunsaturated phospholipid species maintain optimal membrane curvature for Fur4p to evade the Golgi quality control process and to be properly delivered to its normal destination.
Pineau
Ludovic
L
Université de Poitiers, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6161 Transport des assimilats 86022 Poitiers Cedex, France.
Bonifait
Laetitia
L
Berjeaud
Jean-Marc
JM
Alimardani-Theuil
Parissa
P
Bergès
Thierry
T
Ferreira
Thierry
T
D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D004875:Ergosterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D033704:Nucleotide Transport Proteins / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
C035528:FUR4 protein, S cerevisiae; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D033704:Nucleotide Transport Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D004875:Ergosterol