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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002932-13
Application #
3257236
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1979-06-01
Project End
1992-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Kansas State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Manhattan
State
KS
Country
United States
Zip Code
66506
Takemoto, Larry; Sorensen, Christopher M (2008) Protein-protein interactions and lens transparency. Exp Eye Res 87:496-501
Sabah, Judith R; Schultz, Bruce D; Brown, Zach W et al. (2007) Transcytotic passage of albumin through lens epithelial cells. Invest Ophthalmol Vis Sci 48:1237-44
Brown, Zachery; Ponce, Aldo; Lampi, Kirsten et al. (2007) Differential binding of mutant (R116C) and wildtype alphaA crystallin to actin. Curr Eye Res 32:1051-4
Takemoto, Larry J; Ponce, Aldo A (2006) Decreased association of aged alpha crystallins with gamma crystallins. Exp Eye Res 83:793-7
Lin, Dingbo; Barnett, Micheal; Grauer, Laura et al. (2005) Expression of superoxide dismutase in whole lens prevents cataract formation. Mol Vis 11:853-8
Ponce, Aldo; Takemoto, Larry (2005) Screening of crystallin-crystallin interactions using microequilibrium dialysis. Mol Vis 11:752-7
Peterson, James J; Young, Malin M; Takemoto, Larry J (2004) Probing alpha-crystallin structure using chemical cross-linkers and mass spectrometry. Mol Vis 10:857-66
Nguyen, Thu Annelise; Takemoto, Larry J; Takemoto, Dolores J (2004) Inhibition of gap junction activity through the release of the C1B domain of protein kinase Cgamma (PKCgamma) from 14-3-3: identification of PKCgamma-binding sites. J Biol Chem 279:52714-25
Boyle, Daniel L; Takemoto, Larry; Brady, James P et al. (2003) Morphological characterization of the Alpha A- and Alpha B-crystallin double knockout mouse lens. BMC Ophthalmol 3:3
Reddy, V N; Giblin, F J; Lin, L R et al. (2001) Glutathione peroxidase-1 deficiency leads to increased nuclear light scattering, membrane damage, and cataract formation in gene-knockout mice. Invest Ophthalmol Vis Sci 42:3247-55

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