Dove Stephen K, Dong Kangzhen, Kobayashi Takafumi, Williams Fay K, Michell Robert H
School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
Biochem J. 2009 Apr 1;419(1):1-13. doi: 10.1042/BJ20081950.
PtdIns(3,5)P(2) is one of the seven regulatory PPIn (polyphosphoinositides) that are ubiquitous in eukaryotes. It controls membrane trafficking at multiple points in the endosomal/lysosomal system and consequently regulates the size, shape and acidity of at least one endo-lysosomal compartment. PtdIns(3,5)P(2) appears to exert this control via multiple effector proteins, with each effector specific for a subset of the various PtdIns(3,5)P(2)-dependent processes. Some putative PtdIns(3,5)P(2) effectors have been identified, including Atg18p-related PROPPIN [beta-propeller(s) that bind PPIn] proteins and the epsin-like proteins Ent3p and Ent5p, whereas others remain to be defined. One of the principal functions of PtdIns(3,5)P(2) is to regulate the fission/fragmentation of endo-lysosomal sub-compartments. PtdIns(3,5)P(2) is required for vesicle formation during protein trafficking between endo-lysosomes and also for fragmentation of endo-lysosomes into smaller compartments. In yeast, hyperosmotic stress accelerates the latter process. In the present review we highlight and discuss recent studies that reveal the role of the HOPS-CORVET complex and the vacuolar H(+)-ATPase in the process of endo-lysosome fission, and speculate on connections between these machineries and the Fab1p pathway. We also discuss new evidence linking PtdIns(3,5)P(2) and PtdIns5P to the regulation of exocytosis.
磷脂酰肌醇-3,5-二磷酸（PtdIns(3,5)P(2)）是真核生物中普遍存在的七种调节性多磷酸肌醇（PPIn）之一。它在内体/溶酶体系统的多个环节控制膜运输，从而调节至少一个内溶酶体区室的大小、形状和酸度。PtdIns(3,5)P(2)似乎通过多种效应蛋白发挥这种控制作用，每种效应蛋白对各种依赖PtdIns(3,5)P(2)的过程的一个子集具有特异性。一些假定的PtdIns(3,5)P(2)效应蛋白已被鉴定出来，包括与Atg18p相关的PROPPIN（结合PPIn的β-螺旋桨）蛋白以及类epsin蛋白Ent3p和Ent5p，而其他一些仍有待确定。PtdIns(3,5)P(2)的主要功能之一是调节内溶酶体亚区室的分裂/碎片化。在蛋白在内溶酶体之间运输过程中形成囊泡需要PtdIns(3,5)P(2)，并且内溶酶体分裂成较小的区室也需要它。在酵母中，高渗胁迫会加速后一过程。在本综述中，我们重点介绍并讨论了揭示HOPS-CORVET复合物和液泡H(+) -ATP酶在内溶酶体分裂过程中的作用的近期研究，并推测了这些机制与Fab1p途径之间的联系。我们还讨论了将PtdIns(3,5)P(2)和PtdIns5P与胞吐作用调节联系起来的新证据。
