Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane.
Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane.
复制标题
DOI：
10.1042/ebc20200041
复制
发表时间：
2020-09-23
影响因子：
6.4
通讯作者：
Cockcroft S
中科院分区：
文献类型：
--
作者：
Katan M;Cockcroft S
磷脂酰肌醇（4，5）二磷酸（PI（4，5）P2）由于其在细胞膜上的多种功能而成为生物化学、细胞生物学和生理学研究的热点。因此，PI（4，5）P2的功能可以在两个独立且不同的角色中探索-作为磷脂酶C（PLC）和磷酸肌醇3-激酶（PI 3 K）的底物以及作为初级信使，每个都具有独特的性质。因此，PI（4，5）P2在信号转导和细胞过程（包括肌动蛋白细胞骨架动力学、膜动力学和离子通道调节）中起作用。通过质膜G蛋白偶联受体（GPCR）、受体酪氨酸激酶（RTK）和免疫受体的信号传导都使用PI（4，5）P2作为底物来产生第二信使。PI 3 K的活化产生PI（3，4，5）P3（磷脂酰肌醇（3，4，5）三磷酸），其是一种脂质，其募集过多的具有普列克底物蛋白同源性（PH）结构域的蛋白质至质膜以调节细胞功能的多个方面。相比之下，PLC激活导致PI（4，5）P2水解以产生第二信使，二酰基甘油（DAG），蛋白激酶C和肌醇（1，4，5）三磷酸（IP 3/I（1，4，5）P3）的激活剂，其促进细胞内Ca 2+的增加。PLC引起的PI（4，5）P2的减少也影响依赖于完整脂质的功能，因此内吞作用、肌动蛋白动力学和离子通道调节受到控制。PI（4，5）P2在膜处的纳米结构域中的空间组织允许这些多个过程同时发生。
Phosphatidylinositol(4,5) bisphosphate (PI(4,5)P2) has become a major focus in biochemistry, cell biology and physiology owing to its diverse functions at the plasma membrane. As a result, the functions of PI(4,5)P2 can be explored in two separate and distinct roles – as a substrate for phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K) and as a primary messenger, each having unique properties. Thus PI(4,5)P2 makes contributions in both signal transduction and cellular processes including actin cytoskeleton dynamics, membrane dynamics and ion channel regulation. Signalling through plasma membrane G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and immune receptors all use PI(4,5)P2 as a substrate to make second messengers. Activation of PI3K generates PI(3,4,5)P3 (phosphatidylinositol(3,4,5)trisphosphate), a lipid that recruits a plethora of proteins with pleckstrin homology (PH) domains to the plasma membrane to regulate multiple aspects of cellular function. In contrast, PLC activation results in the hydrolysis of PI(4,5)P2 to generate the second messengers, diacylglycerol (DAG), an activator of protein kinase C and inositol(1,4,5)trisphosphate (IP3/I(1,4,5)P3) which facilitates an increase in intracellular Ca2+. Decreases in PI(4,5)P2 by PLC also impact on functions that are dependent on the intact lipid and therefore endocytosis, actin dynamics and ion channel regulation are subject to control. Spatial organisation of PI(4,5)P2 in nanodomains at the membrane allows for these multiple processes to occur concurrently.