Imbalances in the eye lens proteome are linked to cataract formation.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
22
03
2020
accepted:
04
11
2020
pubmed:
13
1
2021
medline:
1
4
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33432246
doi: 10.1038/s41594-020-00543-9
pii: 10.1038/s41594-020-00543-9
doi:
Substances chimiques
Crystallins
0
Molecular Chaperones
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
143-151Commentaires et corrections
Type : CommentIn
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