| First Author | Schmid PWN | Year | 2021 |
| Journal | Nat Struct Mol Biol | Volume | 28 |
| Issue | 2 | Pages | 143-151 |
| PubMed ID | 33432246 | Mgi Jnum | J:339482 |
| Mgi Id | MGI:7522617 | Doi | 10.1038/s41594-020-00543-9 |
| Citation | Schmid PWN, et al. (2021) Imbalances in the eye lens proteome are linked to cataract formation. Nat Struct Mol Biol 28(2):143-151 |
| abstractText | The prevalent model for cataract formation in the eye lens posits that damaged crystallin proteins form light-scattering aggregates. The alpha-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 alpha-, beta-, or gamma-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 alpha-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. |
