A phosphorylation-regulated amphipathic helix controls the membrane translocation and function of the yeast phosphatidate phosphatase
A phosphorylation-regulated amphipathic helix controls the membrane translocation and function of the yeast phosphatidate phosphatase
复制标题
DOI：
10.1073/pnas.1007974107
复制
发表时间：
2010-10-12
影响因子：
11.1
通讯作者：
Siniossoglou, Symeon
中科院分区：
文献类型：
--
作者：
Karanasios, Eleftherios;Han, Gil-Soo;Siniossoglou, Symeon
膜脂质组成的调节对于细胞生长和发育的许多方面至关重要。脂蛋白是一个新的磷脂酸（PA）磷酸酶家族，可从PA产生二酰甘油（DAG），是脂肪代谢、脂肪形成和细胞器生物合成的重要调节因子。脂蛋白转运到膜上的机制在很大程度上是未知的。在这里，我们表明，招聘的酵母脂蛋白（Pah 1 p）的PA水平到核/内质网（ER）膜上的调节。募集需要跨膜蛋白磷酸酶复合物Nem 1 p-Spo 7 p。一旦去磷酸化，Pah 1 p可以通过短的氨基末端两亲性螺旋独立于Nem 1 p-Spo 7 p结合到核/ER膜。去磷酸化增强活性的Pah 1 p，在体外和体内，但只有在存在的功能螺旋。螺旋是磷脂和三酰甘油生物合成所必需的。我们的数据表明，通过Nem 1 p-Spo 7 p复合物使Pah 1 p去磷酸化，使得两亲性螺旋能够将Pah 1 p锚到核/ER膜上，从而允许产生DAG用于脂质生物合成。
Regulation of membrane lipid composition is crucial for many aspects of cell growth and development. Lipins, a novel family of phosphatidate (PA) phosphatases that generate diacylglycerol (DAG) from PA, are emerging as essential regulators of fat metabolism, adipogenesis, and organelle biogenesis. The mechanisms that govern lipin translocation onto membranes are largely unknown. Here we show that recruitment of the yeast lipin (Pah1p) is regulated by PA levels onto the nuclear/endoplasmic reticulum (ER) membrane. Recruitment requires the transmembrane protein phosphatase complex Nem1p-Spo7p. Once dephosphorylated, Pah1p can bind to the nuclear/ER membrane independently of Nem1p-Spo7p via a short amino-terminal amphipathic helix. Dephosphorylation enhances the activity of Pah1p, both in vitro and in vivo, but only in the presence of a functional helix. The helix is required for both phospholipid and triacylglycerol biosynthesis. Our data suggest that dephosphorylation of Pah1p by the Nem1p-Spo7p complex enables the amphipathic helix to anchor Pah1p onto the nuclear/ER membrane allowing the production of DAG for lipid biosynthesis.