Molecular Interactions of Crystallins in the Eye

描述(摘自申请者摘要)：这项资助建议来自 经验丰富的调查员来检查一种突变形式的 αA-晶状体蛋白(R116C)与常染色体显性遗传性白内障 改变了质膜结合升高的性质，因此， 会导致白内障。初步结果显示， 突变的α-晶体蛋白与野生型的α比较，根据P.I.， 这可能是人类常染色体显性遗传白内障的一个致病因素。至 研究常染色体显性遗传性白内障的这种致病因素，3 提出了具体的目标。这些将决定镜片的特性 膜蛋白和脂类与α-晶状体蛋白结合的影响 α-晶状体蛋白翻译后修饰对其膜结合力的影响 突变蛋白在白内障发生中的能力和最终作用 通过建立晶状体表达R116C突变形式的转基因小鼠株系 αA-晶状体蛋白。总之，这些研究将提供关于 αA基因R116C突变在人类常染色体潜在发病机制中的作用 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.