Connexin 50 Regulates Surface Ball-and-Socket Structures and Fiber Cell Organization.
Connexin 50 Regulates Surface Ball-and-Socket Structures and Fiber Cell Organization.
复制标题
DOI：
10.1167/iovs.16-19521
复制
发表时间：
2016-06-01
影响因子：
4.4
通讯作者：
Gong X
中科院分区：
文献类型：
--
作者：
Wang E;Geng A;Maniar AM;Mui BW;Gong X
Gja8编码的间隙连接蛋白connexin 50 （Cx50）在晶状体发育过程中的作用尚不完全清楚。连接蛋白50敲除（KO）晶状体上皮细胞增殖减少，纤维细胞去核改变。我们进一步研究了Cx50 KO （Gja8−/−）晶状体细胞缺陷的机制。采用免疫荧光染色和共聚焦显微镜观察野生型和Cx50型小鼠晶状体膜/细胞骨架蛋白的纤维细胞形态和亚细胞分布。我们观察到Cx50 KO晶状体皮质纤维中存在多种形态缺陷，包括纤维细胞堆积几何形状异常，三细胞顶点f -肌动蛋白富集减少，六边形纤维长侧球窝（BS）结构破坏。此外，在皮质纤维中仅检测到由Cx46 （α3连接蛋白）组成的小间隙连接斑块，并且bs相关的β -糖不良蛋白和ZO-1蛋白的分布发生了改变。连接蛋白50隙连接对脑脊膜结构成熟和皮层纤维细胞组织起重要作用。基于连接蛋白50的间隙连接斑块可能与一系列膜/细胞骨架蛋白形成结构域以稳定BS。Cx50介导的偶联丧失、BS破坏和Cx50 KO纤维中f -肌动蛋白的改变，从而导致小晶状体和轻度白内障表型。
The roles of gap junction protein connexin 50 (Cx50) encoded by Gja8, during lens development are not fully understood. Connexin 50 knockout (KO) lenses have decreased proliferation of epithelial cells and altered fiber cell denucleation. We further investigated the mechanism for cellular defects in Cx50 KO (Gja8−/−) lenses. Fiber cell morphology and subcellular distribution of various lens membrane/cytoskeleton proteins from wild-type and Cx50 KO mice were visualized by immunofluorescent staining and confocal microscopy. We observed multiple morphological defects in the cortical fibers of Cx50 KO lenses, including abnormal fiber cell packing geometry, decreased F-actin enrichment at tricellular vertices, and disrupted ball-and-socket (BS) structures on the long sides of hexagonal fibers. Moreover, only small gap junction plaques consisting of Cx46 (α3 connexin) were detected in cortical fibers and the distributions of the BS-associated beta-dystroglycan and ZO-1 proteins were altered. Connexin 50 gap junctions are important for BS structure maturation and cortical fiber cell organization. Connexin 50–based gap junction plaques likely form structural domains with an array of membrane/cytoskeletal proteins to stabilize BS. Loss of Cx50-mediated coupling, BS disruption, and altered F-actin in Cx50 KO fibers, thereby contribute to the small lens and mild cataract phenotypes.