| First Author | Cheng C | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 52 | Pages | 41187-93 |
| PubMed ID | 20959464 | Mgi Jnum | J:167581 |
| Mgi Id | MGI:4868564 | Doi | 10.1074/jbc.M110.154534 |
| Citation | Cheng C, et al. (2010) Altered chaperone-like activity of alpha-crystallins promotes cataractogenesis. J Biol Chem 285(52):41187-93 |
| abstractText | Despite the enormous number of studies demonstrating changes in the chaperone-like activity of alpha-crystallins in vitro, little is known about how these changes influence life-long lens transparency in vivo. Using the gammaB-crystallin I4F mutant protein as a target for alphaA-crystallins, we examined how cataract phenotypes are modulated by interactions between alpha-crystallins with altered chaperone-like activities and gammaB-I4F proteins in vivo. Double heterozygous alpha-crystallin knock-out alphaA(+/-) alphaB(+/-) mice with a decreased amount of alpha-crystallins were used to simulate reduced total alpha-crystallin chaperone-like activity in vivo. We found that triple heterozygous alphaA(+/-) alphaB(+/-) gammaB(I4F/+) mice developed more severe whole cataracts than heterozygous gammaB(I4F/+) mice. Thus, total chaperone-like activity of alpha-crystallins is important for maintaining lens transparency. We further tested whether mutant alphaA-crystallin Y118D proteins with increased chaperone-like activity influenced the whole cataract caused by the gammaB-I4F mutation. Unexpectedly, compound alphaA(Y118D/+) gammaB(I4F/+) mutant lenses displayed severe nuclear cataracts, whereas the lens cortex remained unaffected. Thus, the synergistic effect of alphaA-Y118D and gammaB-I4F mutant proteins is detrimental to the transparency only in the lens core. alpha-Crystallins with different chaperone-like activities are likely required in the lens cortex and nucleus for maintaining transparency. |
