The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase
The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase
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DOI：
10.1016/s0960-9822(01)00449-3
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发表时间：
2001-09-18
期刊：
影响因子：
9.2
通讯作者：
Mayinger, P
中科院分区：
文献类型：
--
作者：
Schorr, M;Then, A;Mayinger, P
磷脂酰肌醇磷酸酶在基于脂质的信号转导中发挥着重要的作用，但目前还不是很清楚。这些酶的一个亚家族的成员共享一个最初在酵母SAC1蛋白中发现的特定结构域[1]。SAC1同源结构域在体外显示出3-和4-磷酸酶活性[2，3]，除了大鼠和酵母Sac1p外，在酵母Inp/Sjl蛋白[4，5]和哺乳动物突触素[6]中也发现了SAC1同源结构域。尽管对酵母Sac1p的酶特性进行了详细的体外表征，但该蛋白的确切细胞功能仍不清楚。我们在此报道Sac1p在高尔基体运输中具有特定的分泌作用，并作为磷脂酰肌醇4-激酶Pik1p的拮抗剂。Sac1p的消除导致甲壳素合成酶的过度前向运输，从而导致特定的细胞壁缺陷。类似的膜转运缺陷也是由PIK1的过度表达引起的。综上所述，这些发现提供了强有力的证据，证明Ptdlns(4)P的产生足以触发从高尔基体到质膜的前向运输，并且Sac1p是终止这一信号的关键。
Phosphoinositide phosphatases play an essential but as yet not well-understood role in lipid-based signal transduction. Members of a subfamily of these enzymes share a specific domain that was first identified in the yeast Sac1 protein [1]. Sac1 homology domains were shown to exhibit 3- and 4-phosphatase activity in vitro [2, 3] and were also found, in addition to rat and yeast Sac1p, in yeast Inp/Sjl proteins [4, 5] and mammalian synaptojanins [6]. Despite the detailed in vitro characterization of the enzymatic properties of yeast Sac1p, the exact cellular function of this protein has remained obscure. We report here that Sac1p has a specific role in secretion and acts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi trafficking. Elimination of Sac1p leads to excessive forward transport of chitin synthases and thus causes specific cell wall defects. Similar defects in membrane trafficking are caused by the overexpression of PIK1. Taken together, these findings provide strong evidence that the generation of Ptdlns(4)P is sufficient to trigger forward transport from the Golgi to the plasma membrane and that Sac1p is critically required for the termination of this signal.