Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies.
Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies.
复制标题
DOI：
10.1242/jcs.200840
复制
发表时间：
2017-08-01
影响因子：
4
通讯作者：
Nightingale TD
中科院分区：
文献类型：
--
作者：
Stevenson NL;White IJ;McCormack JJ;Robinson C;Cutler DF;Nightingale TD
韦贝尔-帕拉德小体（Webel-Palade bodies，WPB）是内皮细胞的储存细胞器，在正常的止血和炎症反应中起重要作用。它们的主要组成蛋白是血管性血友病因子（VWF），在促分泌素刺激后，VWF作为大的血小板捕获线释放到血管腔中。这种胞吐作用改变了细胞表面的蛋白质组成，也导致质膜数量的净增加。代偿性内吞作用被认为限制了细胞大小的变化，并在胞吐作用后恢复融合机制和其他错位的膜蛋白;然而，对内皮细胞中代偿性内吞作用的程度、时间、机制和精确功能知之甚少。使用生化分析，活细胞成像和相关的旋转盘显微镜和透射电子显微镜分析，我们提供了第一个深入的高分辨率表征这一过程。我们提供了一个补偿性内吞的基础上快速网格蛋白和动力蛋白介导的检索模型。抑制这一过程导致胞吐模式的改变：WPB然后与先前融合的WPB而不是质膜融合，进而导致形成结构受损的缠结VWF串。这篇文章有一个相关的第一人称采访的论文的第一作者。摘要：代偿性内吞在韦伯-帕拉德体胞吐中起关键作用。抑制这一过程导致胞吐模式的改变和血管性血友病因子作为缠结的弦的释放。
Weibel-Palade bodies (WPBs), the storage organelles of endothelial cells, are essential to normal haemostatic and inflammatory responses. Their major constituent protein is von Willebrand factor (VWF) which, following stimulation with secretagogues, is released into the blood vessel lumen as large platelet-catching strings. This exocytosis changes the protein composition of the cell surface and also results in a net increase in the amount of plasma membrane. Compensatory endocytosis is thought to limit changes in cell size and retrieve fusion machinery and other misplaced integral membrane proteins following exocytosis; however, little is known about the extent, timing, mechanism and precise function of compensatory endocytosis in endothelial cells. Using biochemical assays, live-cell imaging and correlative spinning-disk microscopy and transmission electron microscopy assays we provide the first in-depth high-resolution characterisation of this process. We provide a model of compensatory endocytosis based on rapid clathrin- and dynamin-mediated retrieval. Inhibition of this process results in a change of exocytic mode: WPBs then fuse with previously fused WPBs rather than the plasma membrane, leading, in turn, to the formation of structurally impaired tangled VWF strings. This article has an associated First Person interview with the first authors of the paper. Summary: Compensatory endocytosis plays key roles in Weibel-Palade body exocytosis. Inhibition of this process results in a change of exocytic mode and the release of von Willebrand factor as tangled strings.
登录
查看更多内容
影响因子：
16.2
作者：
Hua, Yunfeng;Woehler, Andrew;Klingauf, Juergen
通讯作者：
Klingauf, Juergen
影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
3.8
作者：
DETOLEDO, GA;FERNANDEZ, JM
通讯作者：
FERNANDEZ, JM
冯·维勒布兰德病的分子特征：部分良好。
影响因子：
6.5
作者：
James PD;Lillicrap D
通讯作者：
Lillicrap D
影响因子：
5.5
作者：
Erent, A.;Meli, A.;Carter, T.
通讯作者：
Carter, T.