Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
J Vasc Res. 2021;58(2):65-91. doi: 10.1159/000512618. Epub 2021 Jan 27.
Protein localization in endothelial cells is tightly regulated to create distinct signaling domains within their tight spatial restrictions including luminal membranes, abluminal membranes, and interendothelial junctions, as well as caveolae and calcium signaling domains. Protein localization in endothelial cells is also determined in part by the vascular bed, with differences between arteries and veins and between large and small arteries. Specific protein polarity and localization is essential for endothelial cells in responding to various extracellular stimuli. In this review, we examine protein localization in the endothelium of resistance arteries, with occasional references to other vessels for contrast, and how that polarization contributes to endothelial function and ultimately whole organism physiology. We highlight the protein localization on the luminal surface, discussing important physiological receptors and the glycocalyx. The protein polarization to the abluminal membrane is especially unique in small resistance arteries with the presence of the myoendothelial junction, a signaling microdomain that regulates vasodilation, feedback to smooth muscle cells, and ultimately total peripheral resistance. We also discuss the interendothelial junction, where tight junctions, adherens junctions, and gap junctions all convene and regulate endothelial function. Finally, we address planar cell polarity, or axial polarity, and how this is regulated by mechanosensory signals like blood flow.
蛋白质在血管内皮细胞中的定位受到严格调控，以在其紧密的空间限制内创建不同的信号域，包括腔膜、基底膜、细胞间连接以及 caveolae 和钙信号域。内皮细胞中蛋白质的定位部分取决于血管床，动脉和静脉之间以及大动脉和小动脉之间存在差异。特定的蛋白质极性和定位对于内皮细胞对各种细胞外刺激的反应至关重要。在这篇综述中，我们检查了阻力血管内皮细胞中的蛋白质定位，偶尔会参考其他血管作为对比，以及这种极化如何促进内皮功能并最终影响整个生物体的生理学。我们重点介绍了腔膜表面的蛋白质定位，讨论了重要的生理受体和糖萼。在小阻力血管中，蛋白质向基底膜的极化特别独特，存在肌内皮连接，这是一个信号微域，可调节血管舒张、向平滑肌细胞的反馈，最终影响外周总阻力。我们还讨论了细胞间连接，其中紧密连接、黏附连接和缝隙连接都聚集在一起并调节内皮功能。最后，我们讨论了平面细胞极性或轴向极性，以及血流等机械感觉信号如何调节这种极性。
