D'Angelo Giovanni, Vicinanza Mariella, Di Campli Antonella, De Matteis Maria Antonietta
Laboratory of Secretion Physiopathology, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (CH), Italy.
J Cell Sci. 2008 Jun 15;121(Pt 12):1955-63. doi: 10.1242/jcs.023630.
The phosphoinositides (PIs) are membrane phospholipids that actively operate at membrane-cytosol interfaces through the recruitment of a number of effector proteins. In this context, each of the seven different PI species represents a topological determinant that can establish the nature and the function of the membrane where it is located. Phosphatidylinositol 4-phosphate (PtdIns(4)P) is the most abundant of the monophosphorylated inositol phospholipids in mammalian cells, and it is produced by D-4 phosphorylation of the inositol ring of PtdIns. PtdIns(4)P can be further phosphorylated to PtdIns(4,5)P(2) by PtdIns(4)P 5-kinases and, indeed, PtdIns(4)P has for many years been considered to be just the precursor of PtdIns(4,5)P(2). Over the last decade, however, a large body of evidence has accumulated that shows that PtdIns(4)P is, in its own right, a direct regulator of important cell functions. The subcellular localisation of the PtdIns(4)P effectors initially led to the assumption that the bulk of this lipid is present in the membranes of the Golgi complex. However, the existence and physiological relevance of ;non-Golgi pools' of PtdIns(4)P have now begun to be addressed. The aim of this Commentary is to describe our present knowledge of PtdIns(4)P metabolism and the molecular machineries that are directly regulated by PtdIns(4)P within and outside of the Golgi complex.
磷酸肌醇(PIs)是一类膜磷脂,通过招募多种效应蛋白在膜 - 胞质溶胶界面发挥积极作用。在此背景下,七种不同的PI种类中的每一种都代表一个拓扑决定因素,可决定其所在膜的性质和功能。磷脂酰肌醇4 - 磷酸(PtdIns(4)P)是哺乳动物细胞中最丰富的单磷酸化肌醇磷脂,它由PtdIns肌醇环的D - 4磷酸化产生。PtdIns(4)P可被PtdIns(4)P 5 - 激酶进一步磷酸化为PtdIns(4,5)P(2),事实上,多年来PtdIns(4)P一直被认为只是PtdIns(4,5)P(2)的前体。然而,在过去十年中,大量证据积累表明,PtdIns(4)P本身就是重要细胞功能的直接调节因子。PtdIns(4)P效应器的亚细胞定位最初导致人们认为这种脂质大部分存在于高尔基体复合体的膜中。然而,PtdIns(4)P的“非高尔基体池”的存在及其生理相关性现在已开始得到研究。本述评的目的是描述我们目前对PtdIns(4)P代谢以及高尔基体复合体内外直接受PtdIns(4)P调节的分子机制的认识。