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Vol. 19, Issue 3, 807-821, March 2008

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A Lipid-mediated Quality Control Process in the Golgi Apparatus in Yeast

Ludovic Pineau^*, Laetitia Bonifait, Jean-Marc Berjeaud, Parissa Alimardani-Theuil, Thierry Bergès^*, and Thierry Ferreira^*

*Université de Poitiers, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6161 "Transport des assimilats" and Université de Poitiers, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6008 "Microbiologie fondamentale et appliquée," 86022 Poitiers Cedex, France

Submitted June 22, 2007; Revised November 6, 2007; Accepted December 10, 2007
Monitoring Editor: Sean Munro

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.

Present address: Université de Reims, Faculté des Sciences, "Laboratoire de microbiologie générale et moléculaire," Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France.

Address correspondence to: Thierry Ferreira (thierry.ferreira{at}univ-poitiers.fr)

Abbreviations used: ALA, -aminolevulinate; DRM, detergent-resistant membrane; UFA, unsaturated fatty acids.