Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Physiol Rev. 2013 Jul;93(3):1019-137. doi: 10.1152/physrev.00028.2012.
Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.
磷脂酰肌醇（PIs）仅占细胞磷脂的一小部分，但它们控制着细胞生死的几乎所有方面。这些脂质在 20 世纪 70 年代和 80 年代被发现作为质膜信号分子时引起了极大的研究兴趣。在过去的 15 年中，研究人员发现 PIs 调节了广泛的生物学过程，使这些脂质成为真核细胞中最通用的信号实体之一。PIs 通过调节囊泡运输来控制细胞器生物学，但它们也通过与脂质转移蛋白的密切关系来调节脂质分布和代谢。PIs 调节离子通道、泵和转运蛋白，并控制内吞作用和外排作用。核磷脂酰肌醇已从一个偶然现象发展成为一个独立的研究领域。正如这些多效调节剂所预期的那样，磷脂酰肌醇代谢的紊乱与许多人类疾病有关，从罕见的遗传疾病到最常见的疾病，如癌症、肥胖症和糖尿病。此外，越来越明显的是，许多感染性病原体劫持宿主细胞的 PI 调节系统来进行细胞内运动、复制和组装。因此，PI 转换酶开始被制药公司注意到，作为潜在的治疗靶点。这篇综述试图概述这一巨大的研究领域，重点介绍与细胞生理学和疾病相关的基础科学各个领域的主要进展。
