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Schmid, P.W.N.* ; Lim, N.C.H.* ; Peters, C.* ; Back, K.C.* ; Bourgeois, B.* ; Pirolt, F.* ; Richter, B.* ; Peschek, J.* ; Puk, O. ; Amarie, O.V. ; Dalke, C. ; Haslbeck, M.* ; Weinkauf, S.* ; Madl, T.* ; Graw, J. ; Buchner, J.*

Imbalances in the eye lens proteome are linked to cataract formation.

Nat. Struct. Mol. Biol. 28, 143–151 (2021)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The prevalent model for cataract formation in the eye lens posits that damaged crystallin proteins form light-scattering aggregates. The α-crystallins are thought to counteract this process as chaperones by sequestering misfolded crystallin proteins. In this scenario, chaperone pool depletion would result in lens opacification. Here we analyze lenses from different mouse strains that develop early-onset cataract due to point mutations in α-, β-, or γ-crystallin proteins. We find that these mutant crystallins are unstable in vitro; in the lens, their levels are substantially reduced, and they do not accumulate in the water-insoluble fraction. Instead, all the other crystallin proteins, including the α-crystallins, are found to precipitate. The changes in protein composition and spatial organization of the crystallins observed in the mutant lenses suggest that the imbalance in the lenticular proteome and altered crystallin interactions are the bases for cataract formation, rather than the aggregation propensity of the mutant crystallins.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Alpha-a-crystallin; Gamma-crystallins; Mass-spectrometry; Aggregation; Mutation; Mice; Identification; Transparency; Oxidation; Chaperone
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Journal Nature Structural & Molecular Biology
Quellenangaben Volume: 28, Issue: , Pages: 143–151 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Grants Alexander von Humboldt Foundation
Austrian Science Foundation
Austrian Research Promotion Agency
Integrative Metabolism Research Center Graz
Austrian infrastructure program 2016/2017
Styrian government (Zukunftsfonds)
BioTechMed/Graz
DFG