Sunshine Hannah, Iruela-Arispe Maria Luisa
aMolecular, Cellular and Integrative Physiology Graduate Program bDepartment of Molecular, Cell and Developmental Biology cMolecular Biology Institute, University of California, Los Angeles, California, USA.
Curr Opin Lipidol. 2017 Oct;28(5):408-413. doi: 10.1097/MOL.0000000000000443.
Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last 3 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, and signaling downstream to Toll-like receptor 4 with consequences to nuclear factor kappa B 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.
信号跨质膜的接收与传递通常被认为是跨膜蛋白的功能。然而，在过去三年中，越来越多的报道进一步认识到膜脂在信号转导过程中发挥的重要作用。
特别是，膜脂的组成可以调节具有SH2结构域的蛋白质以及K-Ras等分子如何将其催化结构域暴露于胞质溶胶中，并与效应器和第二信使相互作用。最近的报道还表明，磷脂的饱和程度可以降低某些G蛋白偶联受体的激活，以及Toll样受体4下游的信号传导，从而影响核因子κB的激活和炎症反应。据报道，膜中特定神经节苷脂的水平以细胞自主方式激活整合素，影响肿瘤细胞迁移。此外，胆固醇与 smoothened 受体关联的高分辨率研究阐明了其在音猬因子信号传导中的作用。这些是一些关键进展，进一步推动了我们对膜脂在信号转导中广泛多样作用的理解。
随着我们获得关于脂-蛋白相互作用的影响及其对细胞功能的后果的确切细节，治疗靶点的选择随着更高特异性的可能性而扩大。
