Extensive evidence has strongly suggested that abnormalities in the fiber cell membrane may be involved in human cataractogenesis. This proposal will attempt to correlate changes in membrane protein composition and/or structure, with either known or hypothesized changes in membrane function accompanying human cataractogenesis. Possible changes in gap junction coupling will be correlated with possible structgural changes of the 26K, major gap junction polypeptide. Chemical bifunctional crosslinking reagents, in conjunction with diagonal electrophoresis, will be used for this purpose. Possible changes in membrane protein aggregation will be correlated with further characterization of a membrane-bound 18,000 dalton polypeptide that might be involved in this aggregation. The known decrease in specific activity of the membrane-bound enzyme Na+, K+-ATPase will be correlated with possible changes in amino acid sequence and structure of this enzyme during cataract formation in the human and hereditary mouse model system. Finally, the changes in gap junction coupling, membrane protein aggregation and Na+, K+-ATPase activity will be assessed in the opaque vs. transparent regions of the same cataractous lens. In this way, this study will correlate possible and observed changes in membrane function with the molecular mechanisms responsible for these changes.
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