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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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alpha-a-crystallin; Gamma-crystallins; Mass-spectrometry; Aggregation; Mutation; Mice; Identification; Transparency; Oxidation; Chaperone
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Zeitschrift Nature Structural & Molecular Biology
Quellenangaben Band: 28, Heft: , Seiten: 143–151 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Förderungen 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