Cataract mutation P20S of αB-crystallin impairs chaperone activity of αA-crystallin and induces apoptosis of human lens epithelial cells

详细信息	查看全文 | 推荐本文 |

• 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 //www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">A and //www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small
• 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. sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-crystallin, which is comprised of two homologous subunits, sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">A- and sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">B-crystallin, plays a key role in the maintenance of lens transparency. Recently, we have identified a missense mutation in sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">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 sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-crystallins containing wild type (WT) sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">A in combination with either WT-sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">B- or mutant sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">B-crystallin, respectively. Compared with heteroaggregates of WT-sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">A and WT-sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">B, heteroaggregates containing WT-sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">A and mutant sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">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-sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">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 sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-crystallin complex and cytotoxicity are vital factors in the pathogenesis of congenital cataract linked to the P20S mutation in the sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">B-crystallin.