Rothman J H, Stevens T H
Cell. 1986 Dec 26;47(6):1041-51. doi: 10.1016/0092-8674(86)90819-6.
We have devised a genetic selection for mutant yeast cells that fail to properly deliver the vacuolar glycoprotein CPY to the lysosome-like vacuole. This has allowed us to identify mutations in eight VPL complementation groups that result in aberrant secretion of up to approximately 90% of the immunoreactive CPY. Other soluble vacuolar proteins are also affected by each vpl mutation, demonstrating that a sorting system for multiple vacuolar proteins exists in yeast. Mislocalized CPY apparently traverses late stages of the secretory pathway, since a vesicle-accumulating sec1 mutation prevents secretion of this protein. Despite the presence of abnormal membrane-enclosed organelles in some of the vpl mutants, maturation and secretion of invertase are not substantially perturbed. Thus vpl mutations define a new class of genes that encode products required for sorting of newly synthesized vacuolar proteins from secretory proteins during their transit through the yeast secretory pathway.
我们设计了一种针对突变酵母细胞的遗传筛选方法，这些细胞无法将液泡糖蛋白CPY正确递送至溶酶体样液泡。这使我们能够鉴定出八个VPL互补组中的突变，这些突变导致高达约90%的免疫反应性CPY异常分泌。其他可溶性液泡蛋白也受到每个vpl突变的影响，表明酵母中存在多种液泡蛋白的分选系统。错误定位的CPY显然会穿过分泌途径的后期阶段，因为一个积累囊泡的sec1突变会阻止这种蛋白质的分泌。尽管在一些vpl突变体中存在异常的膜封闭细胞器，但转化酶的成熟和分泌并未受到实质性干扰。因此，vpl突变定义了一类新的基因，这些基因编码在新合成的液泡蛋白通过酵母分泌途径转运过程中，将其与分泌蛋白分选中所需的产物。
