Ankyrin-B is required for the establishment and maintenance of lens cytoarchitecture, mechanics and clarity.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-18 DOI:10.1242/jcs.262349
Rupalatha Maddala, Ariana Allen, Nikolai P Skiba, Ponugoti Vasantha Rao
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Abstract

The transparent ocular lens is essential for vision because it focuses light onto the retina. Despite recognition of the importance of its unique cellular architecture and mechanical properties, the molecular mechanisms governing these attributes remain elusive. This study aims to elucidate the role of ankyrin-B (AnkB, encoded by ANK2), a membrane scaffolding protein, in lens cytoarchitecture, growth and function using a conditional knockout (cKO) mouse model. The AnkB cKO mouse has no defects in lens morphogenesis but exhibited changes that supported a global role for AnkB in maintenance of lens clarity, size, cytoarchitecture, membrane organization and stiffness. Notably, absence of AnkB led to nuclear cataract formation, which was evident from postnatal day 16. AnkB cKO lens fibers exhibit progressive disruption in membrane organization of the spectrin-actin cytoskeleton, cell adhesion proteins and channel proteins; loss and degradation of several membrane proteins [such as NrCAM. N-cadherin (CDH2) and aquaporin-0 (also known as MIP)]; along with a disorganized plasma membrane and impaired membrane interdigitations. Furthermore, absence of AnkB led to decreased lens stiffness. Collectively, these results illustrate the essential role for AnkB in lens architecture, growth and function through its involvement in membrane skeletal and protein organization and stability.

Ankyrin-B 是建立和维持晶状体细胞结构、力学和透明度所必需的。
透明的眼球晶状体能将光线聚焦到视网膜上,对视觉至关重要。尽管人们认识到晶状体独特的细胞结构和机械特性的重要性,但支配这些特性的分子机制仍然难以捉摸。本研究旨在利用条件性基因敲除(cKO)小鼠模型,阐明膜支架蛋白 ankyrin-B(AnkB)在晶状体细胞结构、生长和功能中的作用。AnkB cKO小鼠在晶状体形态发生方面没有缺陷,但表现出的变化支持了AnkB在维持晶状体清晰度、大小、细胞结构、膜组织和硬度方面的整体作用。值得注意的是,AnkB 的缺失会导致核白内障的形成,从 P16 开始就很明显。AnkB cKO 的晶状体纤维表现出谱系蛋白-肌动蛋白细胞骨架、细胞粘附蛋白和通道蛋白的膜组织逐渐破坏,多种膜蛋白(如 NrCAM、N-cadherin 和 aquaporin-0)丢失和降解,同时质膜紊乱,膜间连接受损。此外,缺乏 AnkB 会导致晶状体硬度下降。总之,这些结果说明了 AnkB 通过参与膜骨架和蛋白质的组织与稳定,在晶状体的结构、生长和功能中发挥着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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