Cataract mutation P20S of αB-crystallin impairs chaperone activity of αA-crystallin and induces apoptosis of human lens epithelial cells
- 作者：Hui Li ; Chang Li ; Qiulun Lu ; Ting Su ; Tie Ke ; David Wan-Cheng Li ; Mingxiong Yuan ; Jingyu Liu ; Xiang Ren ; Zhihong Zhang ; Shaoqiong Zeng ; Qing K. Wang ; Mugen Liu
- 关键词：Cataract ; Crystallin
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- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
- 出版年：2008
- 期刊代码：19_09254439
- 类别：bio
- 出版时间：May 2008
- 卷：1782
- 期：5
- 页码：303-309
- 文件大小：1225 K
摘要
Cataract is a common cause of childhood blindness worldwide. 
-crystallin, which is comprised of two homologous subunits, A- and B-crystallin, plays a key role in the maintenance of lens transparency. Recently, we have identified a missense mutation in B-crystallin that changes the proline residue at codon 20 to a serine residue (P20S) in a large Chinese family with autosomal dominant posterior polar congenital cataract. To explore the molecular mechanism by which the P20S mutation causes cataract, we examined the quaternary structure, subunit exchange and chaperone activity of the reconstituted heteroaggregates of -crystallins containing wild type (WT) A in combination with either WT-B- or mutant B-crystallin, respectively. Compared with heteroaggregates of WT-A and WT-B, heteroaggregates containing WT-A and mutant B showed nearly the same molecular mass, but the subunit-exchange rate and chaperone activity were decreased markedly. In human lens epithelial cells, unlike WT-B-crystallin, the P20S mutant protein showed abnormal nuclear localization, and unusual ability to trigger apoptosis. These results suggest that the changes in the structure and function of the -crystallin complex and cytotoxicity are vital factors in the pathogenesis of congenital cataract linked to the P20S mutation in the B-crystallin.
-crystallin, which is comprised of two homologous subunits, A- and B-crystallin, plays a key role in the maintenance of lens transparency. Recently, we have identified a missense mutation in B-crystallin that changes the proline residue at codon 20 to a serine residue (P20S) in a large Chinese family with autosomal dominant posterior polar congenital cataract. To explore the molecular mechanism by which the P20S mutation causes cataract, we examined the quaternary structure, subunit exchange and chaperone activity of the reconstituted heteroaggregates of -crystallins containing wild type (WT) A in combination with either WT-B- or mutant B-crystallin, respectively. Compared with heteroaggregates of WT-A and WT-B, heteroaggregates containing WT-A and mutant B showed nearly the same molecular mass, but the subunit-exchange rate and chaperone activity were decreased markedly. In human lens epithelial cells, unlike WT-B-crystallin, the P20S mutant protein showed abnormal nuclear localization, and unusual ability to trigger apoptosis. These results suggest that the changes in the structure and function of the -crystallin complex and cytotoxicity are vital factors in the pathogenesis of congenital cataract linked to the P20S mutation in the B-crystallin.© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |