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.
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|Srinivas, Pasumarthi; Narahari, Akkaladevi; Petrash, J Mark et al. (2010) Importance of eye lens ?-crystallin heteropolymer with 3:1 ?A to ?B ratio: stability, aggregation, and modifications. IUBMB Life 62:693-702|
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|Hsu, Cheng-Da; Kymes, Steven; Petrash, J Mark (2006) A transgenic mouse model for human autosomal dominant cataract. Invest Ophthalmol Vis Sci 47:2036-44|