Arvcf Dependent Adherens Junction Stability is Required to Prevent Age-Related Cortical Cataracts.
Arvcf Dependent Adherens Junction Stability is Required to Prevent Age-Related Cortical Cataracts.
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DOI：
10.3389/fcell.2022.840129
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
与年龄相关的皮质白内障的病因尚不清楚，但推测与细胞粘附的改变和/或晶状体中随时间发生的机械应力的变化有关。由于充分表征的粘附蛋白在晶状体中具有发育和生理作用，细胞粘附在随着年龄的增长而维持晶状体透明度方面的作用很难评估。该报告表明，Arvcf 是连环蛋白 p120-连环蛋白亚家族的成员，与钙粘蛋白的近膜结构域结合，是一种重要的纤维细胞蛋白，可随着小鼠年龄的增长保持晶状体透明度。在没有 Arvcf 的情况下，没有观察到重大的发育缺陷，然而，所有 6 个月以上接受检查的动物都会出现皮质白内障。虽然幼龄动物的混浊并不明显，但在 4 周后在晶状体中观察到组织学异常，包括纤维细胞分离、六角形晶格混乱区域以及免疫标记膜缺失。整个镜片的压缩分析还表明，Arvcf 是其正常生物力学特性所必需的。对照和 Arvcf 缺陷的晶状体纤维细胞的免疫荧光标记显示 N-钙粘蛋白、β-连环蛋白和 αN-连环蛋白的膜定位减少。此外，超分辨率成像表明蛋白质膜定位的减少与较小的钙粘蛋白纳米簇相关。通过电子显微镜和高分辨率荧光成像对晶状体纤维细胞形态的额外表征还表明，随着钙粘蛋白复合物蛋白定位的减少和瓦解，纤维细胞的细胞突起异常伸长。总之，这些数据表明 Arvcf 需要通过介导粘附连接中 N-钙粘蛋白复合物的稳定性来保持随着年龄增长的透明度。
The etiology of age-related cortical cataracts is not well understood but is speculated to be related to alterations in cell adhesion and/or the changing mechanical stresses occurring in the lens with time. The role of cell adhesion in maintaining lens transparency with age is difficult to assess because of the developmental and physiological roles that well-characterized adhesion proteins have in the lens. This report demonstrates that Arvcf, a member of the p120-catenin subfamily of catenins that bind to the juxtamembrane domain of cadherins, is an essential fiber cell protein that preserves lens transparency with age in mice. No major developmental defects are observed in the absence of Arvcf, however, cortical cataracts emerge in all animals examined older than 6-months of age. While opacities are not obvious in young animals, histological anomalies are observed in lenses at 4-weeks that include fiber cell separations, regions of hexagonal lattice disorganization, and absence of immunolabeled membranes. Compression analysis of whole lenses also revealed that Arvcf is required for their normal biomechanical properties. Immunofluorescent labeling of control and Arvcf-deficient lens fiber cells revealed a reduction in membrane localization of N-cadherin, β-catenin, and αN-catenin. Furthermore, super-resolution imaging demonstrated that the reduction in protein membrane localization is correlated with smaller cadherin nanoclusters. Additional characterization of lens fiber cell morphology with electron microscopy and high resolution fluorescent imaging also showed that the cellular protrusions of fiber cells are abnormally elongated with a reduction and disorganization of cadherin complex protein localization. Together, these data demonstrate that Arvcf is required to maintain transparency with age by mediating the stability of the N-cadherin protein complex in adherens junctions.
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DOI：
10.1085/jgp.201010538
发表时间：
2011-06
期刊：
The Journal of general physiology
影响因子：
--
作者：
Gao J;Sun X;Moore LC;White TW;Brink PR;Mathias RT
通讯作者：
Mathias RT
影响因子：
4.5
作者：
Chen, Yi-ting;Tai, Chin-Yin
通讯作者：
Tai, Chin-Yin
影响因子：
3.5
作者：
Berthoud VM;Minogue PJ;Osmolak P;Snabb JI;Beyer EC
通讯作者：
Beyer EC
影响因子：
16.2
作者：
Elia, Lisa P.;Yamamoto, Miya;Reichardt, Louis F.
通讯作者：
Reichardt, Louis F.
影响因子：
4.4
作者：
Blankenship, Tom;Bradshaw, Linsey;FitzGerald, Paul
通讯作者：
FitzGerald, Paul