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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Autores principales: Kiyotoshi Satoh, Yukitoshi Takemura, Motohiko Satoh, Kiyokazu Ozaki, Shunichiro Kubota
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/c0b8ac297cb349e38c508fc1040412f8
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kiyotoshi Satoh
Yukitoshi Takemura
Motohiko Satoh
Kiyokazu Ozaki
Shunichiro Kubota
Loss of FYCO1 leads to cataract formation
description 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
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