MOLECULAR INTERACTIONS OF CRYSTALLINS IN THE EYE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项拨款建议是由一位经验丰富的研究人员提出的，目的是研究与人类常染色体显性遗传白内障相关的αA-晶状体蛋白(R116C)的突变形式是否改变了质膜结合升高的性质，从而导致白内障。初步结果表明，与野生型α相比，突变型α-晶体蛋白的性质发生了变化，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。为了研究常染色体显性遗传白内障的致病因素，提出了三个具体的研究目标。这些将确定晶状体膜蛋白和脂类在与α-晶状体蛋白结合过程中的特异性，α-晶状体蛋白的翻译后修饰对其膜结合能力的影响，以及通过产生晶状体表达突变形式的α-晶状体蛋白R116C突变形式的小鼠，最终确定突变蛋白在白内障发展中的作用。总之，这些研究将提供关于AlphaA R116C突变在人类常染色体显性遗传白内障潜在机制中的作用的洞察力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.