Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide
Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide
复制标题
钙依赖性膜缔合使可溶性鸟苷酸环化酶对一氧化氮敏感
作者：
U. Zabel;C. Kleinschnitz;P. Oh;P. Nedvetsky;A. Smolenski;H. Müller;Petra Kronich;P. Kugler;U. Walter;J. Schnitzer;H. Schmidt
一氧化氮（NO）是一种普遍存在的、可透过细胞的细胞间信使。目前的概念假设NO通过质膜自由扩散到靶细胞的细胞质中，在那里它激活其胞质受体酶，可溶性鸟苷酸环化酶（sGC）。然而，最近的证据表明，细胞膜不仅是钙依赖性NO合成的主要场所，而且是其分布和结合的场所。在这里，我们将这一概念扩展到NO信号传导，以表明活性sGC在NO敏感性增强的状态下与质膜部分相关。细胞活化后，sGC进一步易位到人血小板中的膜部分，并与大鼠肺内皮细胞中含有NO合酶的小窝部分相关联，其方式依赖于细胞内钙的浓度。我们的数据表明，整个NO信号通路的空间限制比以前假设的，sGC动态易位到质膜，在那里它是敏感的NO。
Nitric oxide (NO) is a ubiquitous, cell-permeable intercellular messenger. The current concept assumes that NO diffuses freely through the plasma membrane into the cytoplasm of a target cell, where it activates its cytosolic receptor enzyme, soluble guanylyl cyclase (sGC). Recent evidence, however, suggests that cellular membranes are not only the predominant site of calcium-dependent NO synthesis, but also the site of its distribution and binding. Here we extend this concept to NO signalling to show that active sGC is partially associated with the plasma membrane in a state of enhanced NO sensitivity. After cellular activation, sGC further translocates to the membrane fraction in human platelets and associates with the NO-synthase-containing caveolar fraction in rat lung endothelial cells, in a manner that is dependent on the concentration of intracellular calcium. Our data suggest that the entire NO signalling pathway is more spatially confined than previously assumed and that sGC dynamically translocates to the plasma membrane, where it is sensitized to NO.
影响因子：
56.9
作者：
VERMA, A;HIRSCH, DJ;SNYDER, SH
通讯作者：
SNYDER, SH
DOI：
10.1073/pnas.93.13.6448
发表时间：
1996-06-25
影响因子：
11.1
作者：
GarciaCardena, G;Oh, P;Sessa, WC
通讯作者：
Sessa, WC
DOI：
10.1073/pnas.88.23.10480
发表时间：
1991-12-01
影响因子：
11.1
作者：
POLLOCK, JS;FORSTERMANN, U;MURAD, F
通讯作者：
MURAD, F