Loss of FYCO1 leads to cataract formation
Abstract Autophagy is a degradation process of cytoplasmic proteins and organelles trafficked to degradation vesicles known as autophagosomes. The conversion of LC3-I to LC3-II is an essential step of autophagosome formation, and FYCO1 is a LC3-binding protein that mediates autophagosome transport....
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Nature Portfolio
2021
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oai:doaj.org-article:c0b8ac297cb349e38c508fc1040412f82021-12-02T16:32:13ZLoss of FYCO1 leads to cataract formation10.1038/s41598-021-93110-12045-2322https://doaj.org/article/c0b8ac297cb349e38c508fc1040412f82021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93110-1https://doaj.org/toc/2045-2322Abstract Autophagy is a degradation process of cytoplasmic proteins and organelles trafficked to degradation vesicles known as autophagosomes. The conversion of LC3-I to LC3-II is an essential step of autophagosome formation, and FYCO1 is a LC3-binding protein that mediates autophagosome transport. The p62 protein also directly binds to LC3 and is degraded by autophagy. In the present study, we demonstrated that disrupting the FYCO1 gene in mice resulted in cataract formation. LC3 conversion decreased in eyes from FYCO1 knockout mice. Further, FYCO1 interacted with αA- and αB-crystallin, as demonstrated by yeast two-hybrid screening and immunoprecipitation analyses. In eyes from knockout mice, the soluble forms of αA- and αB-crystallin, the lens’s major protein components, decreased. In addition, p62 accumulated in eyes from FYCO1 knockout mice. Collectively, these findings suggested that FYCO1 recruited damaged α-crystallin into autophagosomes to protect lens cells from cataract formation.Kiyotoshi SatohYukitoshi TakemuraMotohiko SatohKiyokazu OzakiShunichiro KubotaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Kiyotoshi Satoh Yukitoshi Takemura Motohiko Satoh Kiyokazu Ozaki Shunichiro Kubota Loss of FYCO1 leads to cataract formation |
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Abstract Autophagy is a degradation process of cytoplasmic proteins and organelles trafficked to degradation vesicles known as autophagosomes. The conversion of LC3-I to LC3-II is an essential step of autophagosome formation, and FYCO1 is a LC3-binding protein that mediates autophagosome transport. The p62 protein also directly binds to LC3 and is degraded by autophagy. In the present study, we demonstrated that disrupting the FYCO1 gene in mice resulted in cataract formation. LC3 conversion decreased in eyes from FYCO1 knockout mice. Further, FYCO1 interacted with αA- and αB-crystallin, as demonstrated by yeast two-hybrid screening and immunoprecipitation analyses. In eyes from knockout mice, the soluble forms of αA- and αB-crystallin, the lens’s major protein components, decreased. In addition, p62 accumulated in eyes from FYCO1 knockout mice. Collectively, these findings suggested that FYCO1 recruited damaged α-crystallin into autophagosomes to protect lens cells from cataract formation. |
format |
article |
author |
Kiyotoshi Satoh Yukitoshi Takemura Motohiko Satoh Kiyokazu Ozaki Shunichiro Kubota |
author_facet |
Kiyotoshi Satoh Yukitoshi Takemura Motohiko Satoh Kiyokazu Ozaki Shunichiro Kubota |
author_sort |
Kiyotoshi Satoh |
title |
Loss of FYCO1 leads to cataract formation |
title_short |
Loss of FYCO1 leads to cataract formation |
title_full |
Loss of FYCO1 leads to cataract formation |
title_fullStr |
Loss of FYCO1 leads to cataract formation |
title_full_unstemmed |
Loss of FYCO1 leads to cataract formation |
title_sort |
loss of fyco1 leads to cataract formation |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/c0b8ac297cb349e38c508fc1040412f8 |
work_keys_str_mv |
AT kiyotoshisatoh lossoffyco1leadstocataractformation AT yukitoshitakemura lossoffyco1leadstocataractformation AT motohikosatoh lossoffyco1leadstocataractformation AT kiyokazuozaki lossoffyco1leadstocataractformation AT shunichirokubota lossoffyco1leadstocataractformation |
_version_ |
1718383832829263872 |