Molecular Interactions of Crystallins in the Eye

描述（来自申请人的摘要）：本资助提案来自一个 一位经验丰富的研究人员来研究是否有一种突变形式的 α A-晶状体蛋白（R116 C），与常染色体显性白内障相关， 人，具有改变的升高的质膜结合特性，因此， 引起白内障。初步结果显示， 突变体α-晶状体蛋白与野生型α相比，根据PI， 这可能是人类常染色体显性白内障的致病因素。到 研究常染色体显性白内障的致病因素， 提出了具体目标。这些将决定透镜的特异性 在与α-晶状体蛋白结合过程中， α-晶状体蛋白在其膜结合上的翻译后修饰 突变蛋白在白内障发展中的作用 通过产生用于透镜表达R116 C突变形式的转基因小鼠品系， α A-晶体蛋白总之，这些研究将提供有关 α A R116 C突变体在人常染色体显性遗传潜在机制中的作用 显性白内障

DESCRIPTION (From the Applicant's Abstract): This grant proposal is from a highly experienced investigator to examine whether a mutant form of alphaA-crystallin (R116 C), associated with autosomal dominant cataract in human, has altered property of elevated plasma membrane binding and therefore, causes cataract. Preliminary results shows a change in the property of the mutant alpha-crystallin compared wild type alpha, and according to the P.I., this may be a causative factor in the human autosomal dominant cataract. To investigate this causative factor in the autosomal dominant cataract, three specific aims are proposed. These will determine the specificities of lens membrane proteins and lipids during binding with alpha-crystallin, the effect of post-translational modifications of alpha-crystallin on its membrane-binding capability and finally the role of the mutant protein in cataract development by producing a transgenic mouse strain for lens expression of R116C mutant form of alphaA-crystallin. Together, the studies will provide insight regarding the role of alphaA R116C mutant in potential mechanism of the human autosomal dominant cataract.