Effects of alpha-crystallin on lens cell function and cataract pathology.
The development of cataracts is a debilitating eye condition which is common in elderly patients and afflicts millions worldwide. Cataracts result from the deposition of aggregated proteins in the eye which causes clouding of the lens, light scattering, and obstruction of vision. Non-syndromic, hereditary human cataract development is linked to point mutations in the CRYAA and CRYAB genes which encode alphaA and alphaB-crystallin. The alpha-crystallins are small heat shock proteins which play central roles in maintaining lens transparency and refractive properties. The discovery in 1992 that these proteins possess chaperone-like activity has led most researchers to focus on the ability of alpha-crystallins to prevent protein aggregation in vitro. While the ability of alpha-crystallins to efficiently trap aggregation-prone denatured proteins in vitro is thought to delay the development of age-related cataracts in vivo, alpha-crystallins have additional functions which may also contribute to cataract pathology. In addition to chaperone activity, alpha-crystallins are known to protect cells from stress-induced apoptosis, regulate cell growth, and enhance genomic stability. They also physically and functionally interact with both the cell membrane and cytoskeleton. Functional changes in alpha-crystallin have been shown to modify membrane and cell-cell interactions and lead to lens cell pathology in vivo. This article focuses on the multiple diverse roles of alphaA-crystallin in the maintenance of lens function and cataract development in vivo.
Andley
Usha P
UP
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA. andley@vision.wustl.edu
D000818:Animals; D002386:Cataract / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D042822:Genomic Instability; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D038202:alpha-Crystallin A Chain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D038202:alpha-Crystallin A Chain; D038203:alpha-Crystallin B Chain