紧密连接蛋白occludin和ZO-1作为上皮增殖和存活的调节因子,Annals of the New York Academy of Sciences

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紧密连接蛋白occludin和ZO-1作为上皮增殖和存活的调节因子
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2022-05-17 , DOI: 10.1111/nyas.14798
Wei-Ting Kuo, Matthew A. Odenwald, Jerrold R. Turner, Li Zuo

上皮细胞是粘膜防御的第一道防线。在肠道中，单层上皮细胞必须建立选择性渗透屏障，支持营养吸收和废物分泌，同时防止潜在有害的管腔物质泄漏。其关键是紧密连接，它密封细胞旁空间并防止不受限制的泄漏。紧密连接是由紧密连接蛋白、闭合小带和紧密连接相关 MARVEL 蛋白 (TAMP) 家族成员之间相互作用建立的蛋白质复合物。Claudins 形成冷冻断裂显微镜观察到的特征性紧密连接链，并形成细胞旁通道，但 ZO-1 和 occludin（分别是闭小带和 TAMP 家族的创始成员）的功能尚不清楚。最近的研究表明，这些蛋白质具有重要的非规范（非屏障）功能，使它们能够调节上皮细胞凋亡和增殖，促进病毒进入并组织专门的上皮结构。令人惊讶的是，在没有外源性应激源的情况下，肠道屏障功能或整体健康都不需要这两种物质。在这里，我们简要概述了 ZO-1 和 occludin 规范（与屏障相关）功能，并对它们的非规范功能进行了更详细的检查。

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Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival

Epithelial cells are the first line of mucosal defense. In the intestine, a single layer of epithelial cells must establish a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing the leakage of potentially harmful luminal materials. Key to this is the tight junction, which seals the paracellular space and prevents unrestricted leakage. The tight junction is a protein complex established by interactions between members of the claudin, zonula occludens, and tight junction-associated MARVEL protein (TAMP) families. Claudins form the characteristic tight junction strands seen by freeze-fracture microscopy and create paracellular channels, but the functions of ZO-1 and occludin, founding members of the zonula occludens and TAMP families, respectively, are less well defined. Recent studies have revealed that these proteins have essential noncanonical (nonbarrier) functions that allow them to regulate epithelial apoptosis and proliferation, facilitate viral entry, and organize specialized epithelial structures. Surprisingly, neither is required for intestinal barrier function or overall health in the absence of exogenous stressors. Here, we provide a brief overview of ZO-1 and occludin canonical (barrier-related) functions, and a more detailed examination of their noncanonical functions.

更新日期：2022-05-17

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