Lens Aquaporin 0 Structure in Aging and Cataractogenesis
The Schey lab is interested in examining the posttranslational modifications to the most abundant lens membrane protein, Aquaporin 0 (also known as the lens major intrinsic protein, MIP). Numerous modifications have been identified (see figure) by mass spectrometry. A goal of this research is to determine those modifications which lead to lens opacification through structural studies of human lenses and through functional assays of recombinant modified protein. Additional areas of interest involve protein-protein interactions of lens proteins with Aquaporin 0, changes in the lens membrane proteome with age and cataractogenesis, and lens protein oxidation.
A two dimensional representation of the Human Aquaporin 0 (AQP0) structure indicating sites of truncation (arrows), sites of deamidation (green residues) and sites of phosphorylation (red diamonds).
Confocal microscope image of antiAQP0 labled lens fiber cell membranes.
Related References | Additional Publications
Thibault DB, Gillam CJ, Han J, Schey KL. MALDI Tissue Profiling of Integral Membrane Proteins from Ocular Tissues. J. Amer. Soc. Mass Spectrom., in press.
Grey AC and Schey KL. Distribution of Bovine and Rabbit Lens α-crystallin products by MALDI Imaging Mass Spectrometry. Molecular Vision 14:171-179, 2008.
Lindsey Rose KM, Wang Z, Magrath GN, Hazard ES, Hildebrandt JD and Schey KL. Aquaporin 0-Calmodulin Interaction and the Effect of AQP0 Phosphorylation. Biochemistry, 47:339-47, Jan 8, 2008.
Rose KLM, Gourdie RG, Prescott AR, Quinlan RA, Crouch RK, Schey KL. The C-terminus of lens Aquaporin 0 interacts with the cytoskeletal proteins filensin and CP49. Invest. Ophthalmol. Vis. Sci. 47:1562-70, 2006.
Han J and Schey KL. MALDI tissue imaging of ocular lens α-crystallin. Invest. Ophthalmol. Vis. Sci. 47:2990-6, 2006.
Ervin LA, Ball LE, Crouch RK, Schey KL. Phosphorylation and glycosylation of bovine lens MP20. Invest. Ophthalmol. Vis. Sci. 46(2):627-35, 2005.
Ball LE, Garland DL, Crouch RK, Schey KL. Post-translational modifications of Aquaporin 0 (AQP0) in the normal human lens: spatial and temporal occurrence. Biochemistry 43:9856-65, 2004.
Han J, Schey KL. Proteolysis and mass spectrometric analysis of an integral membrane protein: Aquaporin 0. J. Proteome Res. 3:807-12, 2004. Epub at: http://pubs.acs.org/cgi-bin/asap.cgi/jprobs/asap/pdf/pr049945w.pdf
Han J, Little M, David L, Giblin F, Schey KL. Sequence and peptide map of guinea pig Aquaporin 0. Molecular Vision 10:215-22, 2004.
Ball LE, Little M, Nowak MW, Garland DL, Crouch RK, Schey KL. C-terminally truncated Aquaporin 0 (AQP01-243) observed in the aging human lens remains functionally viable. Invest. Ophthalmol. Vis. Sci. 44:4820-28, 2003.
Schey KL, Little ML, Fowler JG, Crouch RK. Characterization of human lens major intrinsic protein structure. Invest. Ophthalmol. Vis. Sci. 41:175-182, 2000.
Schey KL, Fowler JG, Shearer TR, David L. Modifications to rat lens major intrinsic protein in selenite-induced cataract. Invest. Ophthalmol. Vis. Sci. 40:657-67, 1999.
Schey KL, Fowler JG, Schwartz JC, Busman M, Dillon J, Crouch RK. Complete map and identification of the phosphorylation site of bovine lens MIP. Invest. Ophthalmol. Vis. Sci. 38:2508-15, 1997.
Swamy-Mhruthinti S, Schey KL. Mass spectrometric identification of in vitro glycated sites of MIP. Curr. Eye Res. 16:936-41, 1997.
Lens Protein Oxidation
Roberts JE, Finley EL, Patat SA and Schey KL. Photooxidation of lens proteins with xanthurenic acid: a putative chromophore for cataractogenesis. Photochem. Photobiol. 74:740-44, 2001.
Schey KL and Finley EL. Identification of peptide oxidation by tandem mass spectrometry. Acc. Chem. Res. 33:299-306, 2000.
Schey KL, Patat S, Chignell, CF, Datillo M, Wang RH, Roberts JE. Photooxidation of lens proteins by hypericin (active ingredient in St. John’s Wort). Photochem. Photobiol. 72:200-07, 2000.
Finley EL, Dillon J, Crouch RK, Schey KL. Radiolysis-induced oxidation of bovine α-crystallin. Photochem. Photobiol. 68:9-15, 1998.
Finley EL, Dillon J, Crouch RK, Schey KL. Identification of tryptophan oxidation products in bovine α-crystallin. Prot. Sci. 7:2391-97, 1998.
Finley EL, Busman M, Dillon J, Crouch RK, Schey KL. Identification of photooxidation sites in bovine α-crystallin. Photochem. Photobiol. 66:635-41, 1997.
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