The Sac domain-containing phosphoinositide phosphatases： structure, function, and disease

作     者：FoSheng HSU Yuxin MAO 

作者机构：Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics Cornell University Ithaca NY 14853USA 

出 版 物：《Frontiers in Biology》 (生物学前沿（英文版）)

年 卷 期：2013年第8卷第4期

页      面：395-407页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：supported by grants from NIH:(to Y.M.) funded by the Cornell University Harry Samuel Mann Award (to F.H.) 

主　　题：lipid metabolism membrane trafficking 

摘      要：Phosphoinositides （Pls） have long been known to have an essential role in cell physiology. Their intracellular localization and concentration must be tightly regulated for their proper function. This spatial and temporal regulation is achieved by a large number of PI kinases and phosphatases that are present throughout eukaryotic species. One family of these enzymes contains a conserved PI phosphatase domain termed Sac. Although the Sac domain is homologous among different Sac domain-containing proteins, all appear to exhibit varied substrate specificity and subcellular localization. Dysfunctions in several members of this family are implicated in a range of human diseases such as cardiac hypertrophy, bipolar disorder, Down＇s syndrome, Charcot-Marie-Tooth disease （CMT） and Amyotrophic Lateral Sclerosis （ALS）. In plant, several Sac domain-containing proteins have been implicated in the stress response, chloroplast function and polarized secretion. In this review, we focus on recent findings in the family of Sac domain-containing PI phosphatases in yeast, mammal and plant, including the structural analysis into the mechanism of enzymatic activity, cellular functions, and their roles in disease pathophysiology.