Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431, Fannin Street, Houston, TX.
Traffic. 2018 Mar;19(3):157-165. doi: 10.1111/tra.12541. Epub 2017 Dec 10.
The cell plasma membrane (PM) is a highly dynamic and heterogeneous lipid environment, driven by complex hydrophobic and electrostatic interactions among the hundreds of types of lipid species. Although the biophysical processes governing lipid lateral segregation in the cell PM have been established in vitro, biological implications of lipid heterogeneity are poorly understood. Of particular interest is how membrane proteins potentially utilize transient spatial clustering of PM lipids to regulate function. This review focuses on a lipid-anchored small GTPase K-Ras as an example to explore how its C-terminal membrane-anchoring domain, consisting of a contiguous hexa-lysine polybasic domain and an adjacent farnesyl anchor, possesses a complex coding mechanism for highly selective lipid sorting on the PM. How this lipid specificity modulates K-Ras signal transmission will also be discussed.
细胞质膜（PM）是一个高度动态和异质的脂质环境，由数百种脂质种类之间复杂的疏水和静电相互作用驱动。尽管体外已经确定了控制细胞 PM 中脂质侧向分离的生物物理过程，但脂质异质性的生物学意义还了解甚少。特别有趣的是，膜蛋白如何利用 PM 脂质的瞬时空间聚集来调节功能。本综述以脂质锚定的小 GTPase K-Ras 为例，探讨其 C 末端膜锚定结构域（由连续的六赖氨酸多碱性结构域和相邻的法呢基锚组成）如何具有复杂的编码机制，对 PM 上的高度选择性脂质分选进行编码。还将讨论这种脂质特异性如何调节 K-Ras 信号转导。
