Billaud Marie, Lohman Alexander W, Johnstone Scott R, Biwer Lauren A, Mutchler Stephanie, Isakson Brant E
Dept. of Molecular Physiology and Biophysics, University of Virginia School of Medicine, PO Box 801394, Charlottesville, VA 22902.
Pharmacol Rev. 2014 Mar 26;66(2):513-69. doi: 10.1124/pr.112.007351. Print 2014.
It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.
越来越明显的是，质膜特定区域中蛋白质的积累能够促进细胞通讯。这些区域被称为信号微结构域，存在于整个血管壁中，在血管壁中，细胞内以及不同细胞类型之间的通讯必须受到严格调控，以维持正常的血管功能。我们将定义一个细胞信号微结构域，并将这一定义应用于大量据推测在血管壁中发生细胞通讯的方式。为此，我们提出细胞通讯的三个广泛领域，信号微结构域可能在其中发挥重要作用：1）自由基和气体分子（如一氧化氮和活性氧）的旁分泌释放；2）离子通道（包括缝隙连接和钾通道）的作用，尤其是那些与内皮细胞衍生的超极化介导信号相关的离子通道，最后，3）胞吐作用机制，信号微结构域对其有相当程度的监督，尤其是那些与血管性血友病因子释放相关的信号微结构域。总的来说，我们认为很明显，信号微结构域的组织和调控是血管壁功能的重要组成部分。
