Beverley Katie M, Levitan Irena
Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Front Cell Dev Biol. 2024 Jan 25;12:1352259. doi: 10.3389/fcell.2024.1352259. eCollection 2024.
The purpose of this review is to evaluate the role of cholesterol in regulating mechanosensitive ion channels. Ion channels discussed in this review are sensitive to two types of mechanical signals, fluid shear stress and/or membrane stretch. Cholesterol regulates the channels primarily in two ways: 1) indirectly through localizing the channels into cholesterol-rich membrane domains where they interact with accessory proteins and/or 2) direct binding of cholesterol to the channel at specified putative binding sites. Cholesterol may also regulate channel function via changes of the biophysical properties of the membrane bilayer. Changes in cholesterol affect both mechanosensitivity and basal channel function. We focus on four mechanosensitive ion channels in this review Piezo, Kir2, TRPV4, and VRAC channels. Piezo channels were shown to be regulated by auxiliary proteins that enhance channel function in high cholesterol domains. The direct binding mechanism was shown in Kir2.1 and TRPV4 where cholesterol inhibits channel function. Finally, cholesterol regulation of VRAC was attributed to changes in the physical properties of lipid bilayer. Additional studies should be performed to determine the physiological implications of these sterol effects in complex cellular environments.
本综述的目的是评估胆固醇在调节机械敏感离子通道中的作用。本综述中讨论的离子通道对两种类型的机械信号敏感，即流体剪切应力和/或膜拉伸。胆固醇主要通过两种方式调节这些通道：1）通过将通道定位到富含胆固醇的膜结构域，在那里它们与辅助蛋白相互作用，进行间接调节；和/或2）胆固醇在特定的假定结合位点直接与通道结合。胆固醇还可能通过改变膜双层的生物物理特性来调节通道功能。胆固醇的变化会影响机械敏感性和通道的基础功能。在本综述中，我们重点关注四种机械敏感离子通道，即Piezo、Kir2、TRPV4和VRAC通道。研究表明，Piezo通道受辅助蛋白的调节，这些辅助蛋白在高胆固醇结构域增强通道功能。在Kir2.1和TRPV4中显示了直接结合机制，其中胆固醇抑制通道功能。最后，VRAC的胆固醇调节归因于脂质双层物理性质的变化。应进行更多研究以确定这些固醇效应在复杂细胞环境中的生理意义。
