Tricellulin secures the epithelial barrier at tricellular junctions by interacting with actomyosin.

Tricellulin secures the epithelial barrier at tricellular junctions by interacting with actomyosin.
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DOI:
10.1083/jcb.202009037
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发表时间:
2022-04-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Ikenouchi J
Ikenouchi J
中科院分区:
其他
文献类型:
--
作者:
Cho Y;Haraguchi D;Shigetomi K;Matsuzawa K;Uchida S;Ikenouchi J

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Cho等人揭示,三纤维素将三细胞连接特异性紧密连接链(中心密封元件)与端部锚定到三细胞连接的F-肌动蛋白连接。这使得会聚的中心密封元件保持接近,这有效地闭合了三个上皮细胞之间的差距。上皮细胞片层起屏障作用,防止病原体侵入。不仅在双细胞连接处,而且在三细胞接触处,即三个细胞相遇处,消除细胞间间隙是必要的,以维持上皮屏障功能。为此,相邻细胞之间的紧密连接必须尽可能紧密地结合,特别是在三细胞接触处。三纤维素是三细胞紧密连接(tTJ)的组成部分,但其对上皮屏障功能的分子机制尚不清楚。在这项研究中,我们发现,三纤维素有助于屏障的形成,通过调节肌动球蛋白组织在三细胞连接。此外,我们确定了α-连环蛋白,这被认为是功能只在粘附连接,作为一种新的结合伴侣的三纤维素。α-连环蛋白桥接三细胞蛋白与双细胞肌动蛋白缆的连接,所述双细胞肌动蛋白缆在三细胞连接处端对锚定。因此,三纤维素动员肌动球蛋白收缩性,以关闭会聚在三细胞连接处的三个邻近细胞的TJ链之间的横向间隙。
Cho et al. revealed that tricellulin links tricellular junction–specific tight junction strands, the central sealing elements, with F-actin anchored end-on to tricellular junctions. This enables the converging central sealing elements to remain in proximity, which effectively closes the gap between three epithelial cells. The epithelial cell sheet functions as a barrier to prevent invasion of pathogens. It is necessary to eliminate intercellular gaps not only at bicellular junctions, but also at tricellular contacts, where three cells meet, to maintain epithelial barrier function. To that end, tight junctions between adjacent cells must associate as closely as possible, particularly at tricellular contacts. Tricellulin is an integral component of tricellular tight junctions (tTJs), but the molecular mechanism of its contribution to the epithelial barrier function remains unclear. In this study, we revealed that tricellulin contributes to barrier formation by regulating actomyosin organization at tricellular junctions. Furthermore, we identified α-catenin, which is thought to function only at adherens junctions, as a novel binding partner of tricellulin. α-catenin bridges tricellulin attachment to the bicellular actin cables that are anchored end-on at tricellular junctions. Thus, tricellulin mobilizes actomyosin contractility to close the lateral gap between the TJ strands of the three proximate cells that converge on tricellular junctions.
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