Phospholipid Transfer Protein Sec14 Is Required for Trafficking from Endosomes and Regulates Distinct trans-Golgi Export Pathways
Phospholipid Transfer Protein Sec14 Is Required for Trafficking from Endosomes and Regulates Distinct trans-Golgi Export Pathways
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DOI：
10.1074/jbc.m808732200
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发表时间：
2009-03-13
影响因子：
4.8
通讯作者：
McMaster, Christopher R.
中科院分区：
文献类型：
--
作者：
Curwin, Amy J.;Fairn, Gregory D.;McMaster, Christopher R.
已知调节脂质代谢和囊泡转运的蛋白质是酿酒酵母的磷脂酰胆碱/磷脂酰肌醇转移蛋白Sec 14。Sec 14被认为在全球范围内影响反式高尔基体的分泌。合成基因阵列筛选的结果表明，具有温度敏感性SEC 14等位基因的细胞的失活损害了细胞的生长，这意味着SEC 14调节高尔基体的进出运输。这促使我们研究Sec 14在各种囊泡转运途径中的作用。我们确定Sec 14功能是Bgl 2所遵循的途径所必需的，而其他分泌蛋白，包括Hsp 150，Cts 1，Scw 4，Scw 10，Exg 1，Cis 3和Ygp 1的运输仍然发生，表明Sec 14调节特定的trans-Golgi输出途径。Sec 14功能减弱后，v-SNARE Snc 1在内体和trans-Golgi中积累。其在内体中的蓄积与Sec 14从内体转运至trans-Golgi所需的一致。Sec 14也需要运输Ste 3和亲脂性染料FM 4 -64从质膜到液泡的内体水平。组合的遗传和细胞生物学数据与作为Sec 14的主要作用的内体运输的调节一致。我们进一步确定，脂质配体占用差异调节Sec 14功能。
A protein known to regulate both lipid metabolism and vesicular transport is the phosphatidylcholine/phosphatidylinositol transfer protein Sec14 of Saccharomyces cerevisiae. Sec14 is thought to globally affect secretion from the trans-Golgi. The results from a synthetic genetic array screen for genes whose inactivation impaired growth of cells with a temperature-sensitive SEC14 allele implied Sec14 regulates transport into and out of the Golgi. This prompted us to examine the role of Sec14 in various vesicular transport pathways. We determined that Sec14 function was required for the route followed by Bgl2, whereas trafficking of other secreted proteins, including Hsp150, Cts1, Scw4, Scw10, Exg1, Cis3, and Ygp1, still occurred, indicating Sec14 regulates specific trans-Golgi export pathways. Upon diminution of Sec14 function, the v-SNARE Snc1 accumulated in endosomes and the trans-Golgi. Its accumulation in endosomes is consistent with Sec14 being required for transport from endosomes to the trans-Golgi. Sec14 was also required for trafficking of Ste3 and the lipophilic dye FM4-64 from the plasma membrane to the vacuole at the level of the endosome. The combined genetic and cell biology data are consistent with regulation of endosome trafficking being a major role for Sec14. We further determined that lipid ligand occupancy differentially regulates Sec14 functions.