A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution
A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution
复制标题
DOI：
10.1242/jcs.01157
复制
发表时间：
2004-06-15
影响因子：
4
通讯作者：
Rine, J
中科院分区：
文献类型：
--
作者：
Beh, CT;Rine, J
7个酵母奥什基因（OSH 1-OSH 7）编码哺乳动物氧固醇结合蛋白（OSBP）的直系同源物家族。奥什基因共享至少一个基本的重叠功能，可能与分泌运输和膜脂质组成的调节有关。为了研究奥什基因的重要作用，我们构建了条件性奥什突变体并分析了它们的细胞缺陷。消除所有的奥什功能改变细胞内的甾醇-脂质分布，引起空泡碎片，并导致在细胞质和空泡碎片内的脂滴的积累。奥什蛋白的逐渐耗竭也引起细胞出芽缺陷和异常细胞壁沉积。在奥什突变细胞内吞作用严重受损，但蛋白质运输到液泡和质膜在很大程度上不受影响。其他影响固醇-脂质功能和分布的突变体，即erg 2 Delta和arv 1 Delta，也有类似的缺陷。这些发现表明，奥什基因，通过影响细胞内固醇分布，建立质膜脂质组成，促进内吞作用。
The seven yeast OSH genes (OSH1-OSH7) encode a family of orthologs of the mammalian oxysterol-binding protein (OSBP). The OSH genes share at least one essential overlapping function, potentially linked to the regulation of secretory trafficking and membrane lipid composition. To investigate the essential roles of the OSH genes, we constructed conditional OSH mutants and analyzed their cellular defects. Elimination of all OSH function altered intracellular sterol-lipid distribution, caused vacuolar fragmentation, and resulted in an accumulation of lipid droplets in the cytoplasm and within vacuolar fragments. Gradual depletion of Osh proteins also caused cell budding defects and abnormal cell wall deposition. In OSH mutant cells endocytosis was severely impaired, but protein transport to the vacuole and the plasma membrane was largely unaffected. Other mutants affecting sterol-lipid function and distribution, namely erg2Delta and arv1Delta, shared similar defects. These findings suggested that OSH genes, through effects on intracellular sterol distribution, establish a plasma membrane lipid composition that promotes endocytosis.