The Sac domain-containing phosphoinositide phosphatases: structure, function, and disease.
The Sac domain-containing phosphoinositide phosphatases: structure, function, and disease.
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含 Sac 结构域的磷酸肌醇磷酸酶：结构、功能和疾病。
DOI：
10.1007/s11515-013-1258-y
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发表时间：
2013-08
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磷脂酰肌醇（PI）长期以来一直被认为在细胞生理学中具有重要作用。它们的细胞内定位和浓度必须严格调节以确保其正常功能。这种空间和时间调节是通过存在于整个真核生物物种中的大量PI激酶和磷酸酶来实现的。这些酶中的一个家族含有保守的PI磷酸酶结构域，称为Sac。尽管Sac结构域在不同的含Sac结构域的蛋白质中是同源的，但它们似乎都表现出不同的底物特异性和亚细胞定位。该家族的几个成员的功能障碍涉及一系列人类疾病，如心脏肥大、双相情感障碍、唐氏综合征、腓骨肌萎缩性侧索硬化症（CMT）和肌萎缩性侧索硬化症（ALS）。在植物中，几种含有Sac结构域的蛋白质与胁迫反应、叶绿体功能和极化分泌有关。本文综述了近年来在酵母、哺乳动物和植物中发现的含Sac结构域的PI磷酸酶家族，包括酶的活性机制、细胞功能及其在疾病病理生理中的作用。
Phosphoinositides (PIs) 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.