PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing.
PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing.
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DOI：
10.1038/s42003-023-04706-4
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发表时间：
2023-04-01
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
通过内皮感知剪切应力的两个突出概念是PIEZO 1通道作为机械活化的钙离子进入的介体，以及PECAM 1细胞粘附分子作为具有CDH 5和VGFR 2的三联体的顶点。在这里，我们调查了是否存在关系。通过在小鼠的原生PIEZO 1中插入非破坏性标签，我们揭示了PIEZO 1与PECAM 1的原位重叠。通过重建和高分辨率显微镜研究，我们表明PECAM 1与PIEZO 1相互作用，并将其引导到细胞-细胞连接处。PECAM 1细胞外N-末端在这方面是至关重要的，但与剪切应力连接的C-末端细胞内结构域也有贡献。CDH 5类似地将PIEZO 1驱动到连接处，但与PECAM 1不同，其与PIEZO 1的相互作用是动态的，随着剪切应力的增加而增加。PIEZO 1不与VGFR 2相互作用。PIEZO 1在粘附连接和相关细胞骨架的Ca 2+依赖性形成中是必需的，这与它赋予连接重塑的力依赖性Ca 2+进入一致。这些数据表明PIEZO 1在细胞连接处的汇集，PIEZO 1和PECAM 1机制的结合以及PIEZO 1和粘附分子在根据机械要求定制连接结构中的密切合作。PIEZO 1通道和PECAM 1细胞粘附分子相互作用，并且PIEZO 1在机械应力期间与PECAM 1和CDH 5细胞连接部协作。
Two prominent concepts for the sensing of shear stress by endothelium are the PIEZO1 channel as a mediator of mechanically activated calcium ion entry and the PECAM1 cell adhesion molecule as the apex of a triad with CDH5 and VGFR2. Here, we investigated if there is a relationship. By inserting a non-disruptive tag in native PIEZO1 of mice, we reveal in situ overlap of PIEZO1 with PECAM1. Through reconstitution and high resolution microscopy studies we show that PECAM1 interacts with PIEZO1 and directs it to cell-cell junctions. PECAM1 extracellular N-terminus is critical in this, but a C-terminal intracellular domain linked to shear stress also contributes. CDH5 similarly drives PIEZO1 to junctions but unlike PECAM1 its interaction with PIEZO1 is dynamic, increasing with shear stress. PIEZO1 does not interact with VGFR2. PIEZO1 is required in Ca2+-dependent formation of adherens junctions and associated cytoskeleton, consistent with it conferring force-dependent Ca2+ entry for junctional remodelling. The data suggest a pool of PIEZO1 at cell junctions, the coming together of PIEZO1 and PECAM1 mechanisms and intimate cooperation of PIEZO1 and adhesion molecules in tailoring junctional structure to mechanical requirement. The PIEZO1 channel and the PECAM1 cell adhesion molecule interact and PIEZO1 cooperates with PECAM1 and CDH5 cell junctions during mechanical stress.
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影响因子：
19
作者：
Brasch J;Harrison OJ;Honig B;Shapiro L
通讯作者：
Shapiro L
影响因子：
16.6
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影响因子：
11.1
作者：
Fujiwara, K
通讯作者：
Fujiwara, K
影响因子：
7.7
作者：
Guo YR;MacKinnon R
通讯作者：
MacKinnon R
影响因子：
10.8
作者：
Curd AP;Leng J;Hughes RE;Cleasby AJ;Rogers B;Trinh CH;Baird MA;Takagi Y;Tiede C;Sieben C;Manley S;Schlichthaerle T;Jungmann R;Ries J;Shroff H;Peckham M
通讯作者：
Peckham M