David D, Sundarababu S, Gerst J E
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
J Cell Biol. 1998 Nov 30;143(5):1167-82. doi: 10.1083/jcb.143.5.1167.
Members of the synaptobrevin/VAMP family of v-SNAREs are thought to be essential for vesicle docking and exocytosis in both lower and higher eukaryotes. Here, we describe yeast mutants that appear to bypass the known v-SNARE requirement in secretion. Recessive mutations in either VBM1 or VBM2, which encode related ER-localized membrane proteins, allow yeast to grow normally and secrete in the absence of Snc v-SNAREs. These mutants show selective alterations in protein transport, resulting in the differential trafficking and secretion of certain protein cargo. Yet, processing of the vacuolar marker, carboxypeptidase Y, and the secreted protein, invertase, appear normal in these mutants indicating that general protein trafficking early in the pathway is unaffected. Interestingly, VBM1 and VBM2 are allelic to ELO3 and ELO2, two genes that have been shown recently to mediate the elongation of very long chain fatty acids and subsequent ceramide and inositol sphingolipid synthesis. Thus, the v-SNARE requirement in constitutive exocytosis is abrogated by mutations in early components of the secretory pathway that act at the level of lipid synthesis to affect the ability of secretory vesicles to sort and deliver protein cargo.
突触小泡蛋白/VAMP家族的v-SNARE成员被认为在低等和高等真核生物的囊泡对接和胞吐作用中至关重要。在此，我们描述了似乎绕过分泌过程中已知v-SNARE需求的酵母突变体。编码相关内质网定位膜蛋白的VBM1或VBM2中的隐性突变，使酵母在没有Snc v-SNARE的情况下能够正常生长并分泌。这些突变体在蛋白质运输方面表现出选择性改变，导致某些蛋白质货物的差异运输和分泌。然而，液泡标记物羧肽酶Y和分泌蛋白转化酶的加工在这些突变体中似乎正常，这表明该途径早期的一般蛋白质运输未受影响。有趣的是，VBM1和VBM2与ELO3和ELO2等位，最近已表明这两个基因介导超长链脂肪酸的延长以及随后的神经酰胺和肌醇鞘脂合成。因此，组成型胞吐作用中对v-SNARE的需求被分泌途径早期成分的突变所消除，这些成分在脂质合成水平起作用，以影响分泌囊泡分选和递送蛋白质货物的能力。
