小柯机器人

PLXND1通过改变构象来调节心血管状态
2020-02-10 09:55

英国牛津大学Ellie Tzima课题组研究发现引导受体plexin D1是内皮细胞的机械传感器。202025日,《自然》在线发表了这项成果。

研究表示plexin D1PLXND1)在机械感觉和机械诱导的疾病发病机理中发挥作用。 PLXND1是内皮细胞在体外和体内应答剪切力所必需的,并调节动脉粥样硬化病变的位点特异性分布。在内皮细胞中,PLXND1是直接力传感器,与Neuropilin-1VEGFR2形成机械复合体,这对于赋予连接复合体和整联蛋白上游机械敏感性是必要的和充分的。PLXND1通过采用两种不同的分子构象来实现其作为配体或力受体的二元功能。他们的研究结果在内皮细胞中建立了以前未描述的机械传感器,该传感器可调节心血管的病理生理,并提供一种利用单个受体发挥二元生化特性的机制。

据了解,血流产生的动脉剪切力对于血管发育和体内平衡很重要,但也会引发动脉粥样硬化。排列在脉管系统中的内皮细胞利用分子机械传感器直接检测剪切力图谱,最终导致抗动脉粥样硬化或动脉粥样硬化反应。plexin是信号导向蛋白信号蛋白家族的关键细胞表面受体,可以通过调节细胞骨架和粘附蛋白结构来调节细胞模式。但是,plexin蛋白在机械转导中的作用尚不清楚。

附:英文原文

Title: The guidance receptor plexin D1 is a mechanosensor in endothelial cells

Author: Vedanta Mehta, Kar-Lai Pang, Daniel Rozbesky, Katrin Nather, Adam Keen, Dariusz Lachowski, Youxin Kong, Dimple Karia, Michael Ameismeier, Jianhua Huang, Yun Fang, Armando del Rio Hernandez, John S. Reader, E. Yvonne Jones, Ellie Tzima

Issue&Volume: 2020-02-05

Abstract: Shear stress on arteries produced by blood flow is important for vascular development and homeostasis but can also initiate atherosclerosis1. Endothelial cells that line the vasculature use molecular mechanosensors to directly detect shear stress profiles that will ultimately lead to atheroprotective or atherogenic responses2. Plexins are key cell-surface receptors of the semaphorin family of cell-guidance signalling proteins and can regulate cellular patterning by modulating the cytoskeleton and focal adhesion structures3,4,5. However, a role for plexin proteins in mechanotransduction has not been examined. Here we show that plexin D1 (PLXND1) has a role in mechanosensation and mechanically induced disease pathogenesis. PLXND1 is required for the response of endothelial cells to shear stress in vitro and in vivo and regulates the site-specific distribution of atherosclerotic lesions. In endothelial cells, PLXND1 is a direct force sensor and forms a mechanocomplex with neuropilin-1 and VEGFR2 that is necessary and sufficient for conferring mechanosensitivity upstream of the junctional complex and integrins. PLXND1 achieves its binary functions as either a ligand or a force receptor by adopting two distinct molecular conformations. Our results establish a previously undescribed mechanosensor in endothelial cells that regulates cardiovascular pathophysiology, and provide a mechanism by which a single receptor can exhibit a binary biochemical nature.

DOI: 10.1038/s41586-020-1979-4

Source: https://www.nature.com/articles/s41586-020-1979-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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