Loss of FYCO1 leads to cataract formation

Kiyotoshi Satoh,Kiyokazu Ozaki,Yukitoshi Takemura,Shunichiro Kubota,Motohiko Satoh

doi:10.1038/s41598-021-93110-1

Kiyotoshi Satoh, Kiyokazu Ozaki + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-93110-1

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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.

Highlights

Autophagy is a degradation process of cytoplasmic proteins and organelles trafficked to degradation vesicles known as autophagosomes
To generate FYVE and coiled-coil [CC] domain containing 1 (FYCO1) KO mice mouse FYCO1 gene was disrupted by the insertion of a neomycin resistance gene cassette (Neo) in the first coding exon
We demonstrated that disruption of the FYCO1 gene in mice caused cataract formation

Summary

Introduction

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. In eyes from knockout mice, the soluble forms of αA- and αB-crystallin, the lens’s major protein components, decreased. P62 accumulated in eyes from FYCO1 knockout mice These findings suggested that FYCO1 recruited damaged α-crystallin into autophagosomes to protect lens cells from cataract formation. Abbreviations FYCO1 FYVE and coiled-coil [CC] domain containing 1 LC3 Microtubule-associated protein 1 light chain 3 OFZ Organelle free zone DAPI 4′,6-Diamino-2-phenylindole MEF Mouse embryonic fibroblasts WT and KO mouse Wild-type and knockout mouse ATG Autophagy-related PVDF Polyvinylidene difluoride KO Knockout WT Wild type. Autophagy plays a pivotal role in lens fiber cell maturation and the formation of the organelle free zone (OFZ).

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