Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9.
Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9.
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DOI：
10.1083/jcb.146.1.125
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发表时间：
1999-07-12
期刊：
影响因子：
--
通讯作者：
Brennwald P
中科院分区：
文献类型：
--
作者：
Lehman K;Rossi G;Adamo JE;Brennwald P
我们已经确定了一对相关的酵母蛋白，Sro 7 p和Sro 77 p，基于它们与质膜SNARE（SNARE）蛋白Sec 9 p结合的能力。这些蛋白质显示出与果蝇肿瘤抑制因子致死性巨幼虫和神经元突触融合蛋白结合蛋白tomosyn的显著相似性。SRO 7和SRO 77具有冗余功能，因为这两种基因产物的缺失导致与胞吐中的严重缺陷相关的严重冷敏感性生长缺陷。我们发现，类似于Sec 9，Sro 7/77的功能在高尔基体后囊泡与质膜的对接和融合。与以前的报告相反，我们没有看到缺陷的肌动蛋白极性的条件下，我们看到一个显着的影响分泌。这表明，Sro 7/77的主要功能，可能是致命的巨型幼虫家族的所有成员，是在胞吐，而不是在调节肌动蛋白细胞骨架。Sro 7 p和Sec 9 p的关联的分析表明，Sro 7 p直接与Sec 9 p在细胞质溶胶和质膜中相互作用，并且可以在SNAP受体复合物的背景下与Sec 9 p相关联。遗传分析表明，Sro 7和Sec 9在Rho 3 GT3下游的通路中一起起作用。总之，我们的研究表明，致命的巨型幼虫/tomosyn/Sro 7家族的成员通过调节质膜上的SNARE功能在极化胞吐中发挥重要作用。
We have identified a pair of related yeast proteins, Sro7p and Sro77p, based on their ability to bind to the plasma membrane SNARE (SNARE) protein, Sec9p. These proteins show significant similarity to the Drosophila tumor suppressor, lethal giant larvae and to the neuronal syntaxin–binding protein, tomosyn. SRO7 and SRO77 have redundant functions as loss of both gene products leads to a severe cold-sensitive growth defect that correlates with a severe defect in exocytosis. We show that similar to Sec9, Sro7/77 functions in the docking and fusion of post-Golgi vesicles with the plasma membrane. In contrast to a previous report, we see no defect in actin polarity under conditions where we see a dramatic effect on secretion. This demonstrates that the primary function of Sro7/77, and likely all members of the lethal giant larvae family, is in exocytosis rather than in regulating the actin cytoskeleton. Analysis of the association of Sro7p and Sec9p demonstrates that Sro7p directly interacts with Sec9p both in the cytosol and in the plasma membrane and can associate with Sec9p in the context of a SNAP receptor complex. Genetic analysis suggests that Sro7 and Sec9 function together in a pathway downstream of the Rho3 GTPase. Taken together, our studies suggest that members of the lethal giant larvae/tomosyn/Sro7 family play an important role in polarized exocytosis by regulating SNARE function on the plasma membrane.
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