In vivo substrates of the lens molecular chaperones αA-crystallin and αB-crystallin
| العنوان: | In vivo substrates of the lens molecular chaperones αA-crystallin and αB-crystallin |
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| المؤلفون: | James P. Malone, Usha P. Andley, Raymond R. Townsend |
| المصدر: | PLoS ONE, Vol 9, Iss 4, p e95507 (2014) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Proteomics, Mutant, Alpha-Crystallin A Chain, Muscle Proteins, lcsh:Medicine, Research and Analysis Methods, Biochemistry, alpha-Crystallin A Chain, Mass Spectrometry, Phosphoglycerate mutase, 03 medical and health sciences, Mice, Model Organisms, Intermediate Filament Proteins, Crystallin, Heat shock protein, Lens, Crystalline, Medicine and Health Sciences, Animals, Eye Proteins, lcsh:Science, Gelsolin, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Multidisciplinary, biology, Calpain, 030302 biochemistry & molecular biology, lcsh:R, Wild type, Biology and Life Sciences, Proteins, alpha-Crystallin B Chain, Crystallins, Mice, Mutant Strains, eye diseases, Ophthalmology, Chaperone (protein), Lens Disorders, biology.protein, lcsh:Q, sense organs, Research Article |
| الوصف: | αA-crystallin and αB-crystallin are members of the small heat shock protein family and function as molecular chaperones and major lens structural proteins. Although numerous studies have examined their chaperone-like activities in vitro, little is known about the proteins they protect in vivo. To elucidate the relationships between chaperone function, substrate binding, and human cataract formation, we used proteomic and mass spectrometric methods to analyze the effect of mutations associated with hereditary human cataract formation on protein abundance in αA-R49C and αB-R120G knock-in mutant lenses. Compared with age-matched wild type lenses, 2-day-old αA-R49C heterozygous lenses demonstrated the following: increased crosslinking (15-fold) and degradation (2.6-fold) of αA-crystallin; increased association between αA-crystallin and filensin, actin, or creatine kinase B; increased acidification of βB1-crystallin; increased levels of grifin; and an association between βA3/A1-crystallin and αA-crystallin. Homozygous αA-R49C mutant lenses exhibited increased associations between αA-crystallin and βB3-, βA4-, βA2-crystallins, and grifin, whereas levels of βB1-crystallin, gelsolin, and calpain 3 decreased. The amount of degraded glutamate dehydrogenase, α-enolase, and cytochrome c increased more than 50-fold in homozygous αA-R49C mutant lenses. In αB-R120G mouse lenses, our analyses identified decreased abundance of phosphoglycerate mutase, several β- and γ-crystallins, and degradation of αA- and αB-crystallin early in cataract development. Changes in the abundance of hemoglobin and histones with the loss of normal α-crystallin chaperone function suggest that these proteins also play important roles in the biochemical mechanisms of hereditary cataracts. Together, these studies offer a novel insight into the putative in vivo substrates of αA- and αB-crystallin. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::182e1917ebf0f4ddafd0ba7c566e8396Test http://europepmc.org/articles/PMC3997384?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....182e1917ebf0f4ddafd0ba7c566e8396 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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