Membrane lipids and cell signaling.
Membrane lipids and cell signaling.
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膜脂质和细胞信号传导。
DOI：
10.1097/mol.0000000000000443
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发表时间：
2017-10
影响因子：
4.4
通讯作者：
Iruela-Arispe ML
中科院分区：
文献类型：
--
作者：
Sunshine H;Iruela-Arispe ML
跨质膜的信号接收和传输通常归因于跨膜蛋白的功能。然而近三年来，越来越多的报道进一步承认膜脂在信号转导过程中发挥的重要贡献。特别是，膜脂的成分可以调节具有 SH2 结构域的蛋白质和 K-Ras 等分子如何将其催化结构域暴露于胞质溶胶并与效应子和第二信使相互作用。最近的报告还表明，磷脂的饱和度可以减少某些 G 蛋白偶联受体的激活，以及 Toll 样受体 4 下游的信号传导，从而导致 NFkB 激活和炎症。据报道，膜中特定神经节苷脂的水平会以细胞自主的方式激活整合素，从而影响肿瘤细胞的迁移。此外，胆固醇与 Smoothened 受体关联的高分辨率阐明了其参与声波刺猬信号传导。这些关键进展进一步推动了我们对膜脂在信号转导中广泛用途的理解。随着我们获得有关脂质-蛋白质相互作用的影响及其对细胞功能的影响的明确细节，治疗靶向的选择范围扩大，并具有更高特异性的可能性。
Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last three years, however, a growing number of reports have further acknowledged important contributions played by membrane lipids in the process of signal transduction. In particular, the constituency of membrane lipids can regulate how proteins with SH2 domains and molecules like K-Ras expose their catalytic domains to the cytosol and interact with effectors and second messengers. Recent reports have also shown that the degree of saturation of phospholipids can reduce the activation of certain G-protein coupled receptors, as well as signaling downstream to Toll-like receptor 4 with consequences to NFkB activation and inflammation. Levels of specific gangliosides in the membrane were reported to activate integrins in a cell-autonomous manner affecting tumor cell migration. Furthermore, high resolution of the association of cholesterol with the Smoothened receptor has clarified its participation in sonic hedgehog signaling. These are some of the key advancements that have further propelled our understanding of the broad versatile contributions of membrane lipids in signal transduction. As we gain definitive detail regarding the impact of lipid-protein interactions and their consequences to cell function, the options for therapeutic targeting expand with the possibility of greater specificity.