Pineau Ludovic, Bonifait Laetitia, Berjeaud Jean-Marc, Alimardani-Theuil Parissa, Bergès Thierry, Ferreira Thierry
Université de Poitiers, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6161 Transport des assimilats 86022 Poitiers Cedex, France.
Mol Biol Cell. 2008 Mar;19(3):807-21. doi: 10.1091/mbc.e07-06-0600. Epub 2007 Dec 19.
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.
当血红素生物合成受到干扰时，酿酒酵母无法合成其主要固醇麦角固醇，也无法使脂肪酸去饱和。我们利用这一生理特性来评估麦角固醇和/或不饱和脂肪酸（UFA）耗竭对一种多跨膜质膜蛋白——尿嘧啶通透酶Fur4p生物合成的影响。我们发现，在导致二不饱和磷脂种类含量低的UFA短缺情况下以及在麦角固醇耗竭情况下，Fur4p会在一个需要泛素连接酶Rsp5p的过程中过早地从高尔基体转运至液泡腔。有趣的是，这种转向与Fur4p被排除在抗去污剂膜之外并无关联。在另一组独立实验中，我们表明Fur4p靶向质膜取决于磷脂酰乙醇胺的含量，更具体地说，取决于这种磷脂形成六方相的倾向。根据最近的文献，我们提出了一个模型，其中麦角固醇和二不饱和磷脂种类维持最佳膜曲率，以使Fur4p逃避高尔基体质量控制过程并被正确地转运至其正常目的地。
