Schorr M, Then A, Tahirovic S, Hug N, Mayinger P
Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
Curr Biol. 2001 Sep 18;11(18):1421-6. doi: 10.1016/s0960-9822(01)00449-3.
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 PtdIns(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.
磷酸肌醇磷酸酶在基于脂质的信号转导中发挥着至关重要但尚未完全理解的作用。这些酶的一个亚家族成员共享一个特定结构域，该结构域最初是在酵母Sac1蛋白中鉴定出来的[1]。已证明Sac1同源结构域在体外具有3-磷酸酶和4-磷酸酶活性[2,3]，并且除了大鼠和酵母Sac1p之外，还在酵母Inp/Sjl蛋白[4,5]和哺乳动物突触素[6]中发现。尽管对酵母Sac1p的酶学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。我们在此报告，Sac1p在分泌中具有特定作用，并在高尔基体运输中作为磷脂酰肌醇4-激酶Pik1p的拮抗剂。Sac1p的缺失导致几丁质合成酶的过度正向运输，从而导致特定的细胞壁缺陷。PIK1的过表达也会导致膜运输出现类似缺陷。综上所述，这些发现提供了强有力的证据，即磷脂酰肌醇-4-磷酸（PtdIns(4)P）的生成足以触发从高尔基体到质膜的正向运输，并且Sac1p是终止该信号的关键因素。
