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MSRC Schey Lab

Lens Aquaporin 0 Structure in Aging and Cataractogenesis

The Schey lab has discovered the majority of the posttranslational modifications (PTMs) known to be present on the most abundant lens membrane protein, Aquaporin 0 (A.K.A. lens major intrinsic protein, MIP, or MP26) by using a variety of proteomics approaches. 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.

Most recently, immunohistochemistry and direct tissue profiling & imaging have been employed to acquire spatially-resolved information on PTMs in the lens (see Imaging Mass Spectrometry).

Related lens work includes studies of other membrane proteins including gap junctional proteins (connexins 46 & 50) and MP20 (or LIM2) as well as cytoskeletal proteins (filensin and CP49) and crystallins.


 

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).

Immunofluorescence image of antiAQP0 labeled lens fiber cell membranes.

Related References

Wang Z, Lyons B, Truscott RJW, Schey KL. Human Protein Aging: Modification and Crosslinking through Dehydroalanine and Dehydrobutyrine Intermediates. Aging Cell, 13:226-234, 2014.

Schey KL, Wang Z, Wenke J, Qi Y. Aquaporins in the Eye: Expression, Function, and Roles in Ocular Disease. Biochim. Biophys. Acta, 1840:1513-1523, 2014.

Schey KL, Grey AC, Nicklay JJ. Mass Spectrometry Analysis of Membrane Proteins: A Focus on Aquaporins, Biochemistry, 52:3807-3817, 2013.

Maddala R, Nagendran T, de Ridder GG, Schey KL, Rao PV. L-Type Calcium Channels Play a Critical Role in Maintaining Lens Transparency by Regulating Phosphorylation of Aquaporin-0 and Myosin Light Chain and Expression of Connexins, PLoS One, 8:e64676, 2013.

Wang Z, Han J, David LL, Schey KL. Proteomics and Phosphoproteomics Analysis of Human Lens Fiber Cell Membranes, Invest. Ophthalmol. Vis. Sci. 54:1135-1143, 2013.

Schey KL, Grey AC, Nicklay JJ. Mass Spectrometry Analysis of Membrane Proteins: A Focus on Aquaporins, Biochemistry, 52:3807-3817, 2013.

Grey, AC, Walker KL, Petrova RS, Han J, Wilmarth PA, David LL, Donaldson PJ, Schey KL. Verification and Spatial Localization of Aquaporin-5 in the Ocular Lens. Exp. Eye Res. 108:94-102, 2013.

Gutierrez DB, Garland D, Schey KL. Spatial analysis of human lens aquaporin-0 post-translational modifications by MALDI mass spectrometry tissue profiling, Exp. Eye Res., 93:912-920, 2011.

Truscott RJW, Comte-Walters S, Ablonczy A, Schwacke JH, Berry Y, Korlimbinis A, Friedrich MG, Schey KL. Tight binding of proteins to membranes from older human cells. AGE, 33:543-54, 2011.

Wang Z and Schey KL. Aquaporin-0 interacts with the FERM domain of ERM proteins in the ocular lens, Invest. Ophthalmol. Vis. Sci. 52:5079-5087, 2011.

Schey KL, Wang Z, Gutierrez DB, Wei J, Grey AC. Novel fatty acid acylation of lens integral membrane protein aquaporin-0. Biochemistry 49:9858-9865, 2010.

Wang Z, Obidike JE, Schey KL. Posttranslational Modifications of Bovine Lens Beaded Filament Proteins Filensin and CP49. Invest. Ophthalmol. Vis. Sci., 51:1565-74, 2010.

Wang Z and Schey KL. Phosphorylation and Truncation Sites of Bovine Lens Connexin 46 and Connexin 50, Exp. Eye Res., 89:898-904, 2009.

Grey AC, Li L, Jacobs MD, Schey KL, Donaldson PJ. Differentiation-dependent Modification and Sub-cellular Distribution of Aquaporin-0 Suggests Multiple Functional Roles in the Rat Lens, Differentiation, 77:70-83, 2009.

Korlimbinus A, Berry Y, Thibault D, Schey KL, Truscott RJW: Protein aging: Truncation of aquaporin 0 in human lens regions is an age dependent process that may contribute to barrier formation, Exp. Eye Res. 88:966-973, 2009.

Grey AC, Chaurand P, Caprioli, RM , Schey KL. MALDI Imaging Mass Spectrometry of Integral Membrane Proteins from Ocular Lens and Retinal Tissue, J. Proteom. Res., 8:3278-3283, 2009.

Lim J, Walker K, Sherwin T, Schey KL, Donaldson P. Confocal Microscopy Reveals a Zone of Membrane Remodelling in the Outer Cortex of the Human Lens, Invest. Ophthalmol. Vis. Sci., 50:4304-4310, 2009.

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, 2008, 47:339-347.

Thibault DB, Gillam CJ, Han J, Schey KL. MALDI Tissue Profiling of Integral Membrane Proteins from Ocular Tissues, J. Amer. Soc. Mass Spectrom., 19:814-22, 2008.

Wang Z, Han J, Schey KL. Spatial Differences in an Integral Membrane Proteome Detected in Laser Capture Microdissected Samples, J. Proteome Res., 7:2696-702, 2008.

Rose KML, Gourdie RG, Prescott AR, Quinlan RA, Crouch RK and Schey KL. The C-terminus of lens aquaporin 0 interacts with the cytoskeletal proteins filensin and CP49, Invest Ophthalmol Vis Sci, 2006, 47:1562-1570.

Ervin LA, Ball LE, Crouch RK, Schey KL: Phosphorylation and Glycosylation of Bovine Lens MP20. Invest. Ophthalmol Vis Sci, 2005, 46:627-635.

Han J, and Schey KL. Proteolysis and mass spectrometric analysis of an integral membrane protein: Aquaporin 0. J Proteome Res., 2004, 3:807-812.

Ball LE, Garland DL, Crouch RK and Schey KL. Post-translational modifications of aquaporin 0 (AQP0) in the normal human lens: Spatial and temporal occurrence. Biochemistry 2004, 43:9856-9865.

Han J, Little M, David LL, Giblin FJ, and Schey KL. Sequence and peptide map of guinea pig aquaporin 0. Mol. Vis., 2004, 10:215-222.

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., 2003, 44:4820-4828.

Schey KL, Little ML, Fowler JG, Crouch RK: Characterization of Human Lens Major Intrinsic Protein Structure, Invest. Ophthalmol. Vis. Sci., 2000, 41:175-182.

Schey KL, Fowler JG, Shearer TR, David L: Modifications to Rat Lens Major Intrinsic Protein in Selenite-Induced Cataract, Invest. Ophthalmol. Vis. Sci., 1999, 40:657-667.

Swamy-Mhruthinti S, Schey KL: Mass Spectrometric Identification of In Vitro Glycated Sites of MIP. Curr. Eye Res., 1997, 16:936-941.

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., 1997, 38:2508-2515.

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