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The role of FYCO1-dependent autophagy in lens fiber cell differentiation

Autophagy, 2022-09, Vol.18 (9), p.2198-2215 [Peer Reviewed Journal]

2022 Informa UK Limited, trading as Taylor & Francis Group 2022 ;2022 Informa UK Limited, trading as Taylor & Francis Group 2022 Informa UK Limited, trading as Taylor & Francis Group ;ISSN: 1554-8627 ;EISSN: 1554-8635 ;DOI: 10.1080/15548627.2022.2025570 ;PMID: 35343376

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Title:
The role of FYCO1-dependent autophagy in lens fiber cell differentiation
Author: Khan, Shahid Y. ; Ali, Muhammad ; Kabir, Firoz ; Na, Chan Hyun ; Delannoy, Michael ; Ma, Yinghong ; Qiu, Caihong ; Costello, M. Joseph ; Hejtmancik, J. Fielding ; Riazuddin, S. Amer
Subjects: Animals ; Autophagy ; Cataract - genetics ; Cataract - metabolism ; cataracts ; Cell Differentiation ; Endoplasmic Reticulum - metabolism ; Humans ; lens fiber cells ; Lens, Crystalline - metabolism ; Mice ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; organelle removal ; organelle-free zone ; Research Paper ; Transcription Factors - metabolism
Is Part Of: Autophagy, 2022-09, Vol.18 (9), p.2198-2215
Description: FYCO1 (FYVE and coiled-coil domain containing 1) is an adaptor protein, expressed ubiquitously and required for microtubule-dependent, plus-end-directed transport of macroautophagic/autophagic vesicles. We have previously shown that loss-of-function mutations in FYCO1 cause cataracts with no other ocular and/or extra-ocular phenotype. Here, we show fyco1 homozygous knockout (fyco1 −/− ) mice recapitulate the cataract phenotype consistent with a critical role of FYCO1 and autophagy in lens morphogenesis. Transcriptome coupled with proteome and metabolome profiling identified many autophagy-associated genes, proteins, and lipids respectively perturbed in fyco1 −/− mice lenses. Flow cytometry of FYCO1 (c.2206C>T) knock-in (KI) human lens epithelial cells revealed a decrease in autophagic flux and autophagic vesicles resulting from the loss of FYCO1. Transmission electron microscopy showed cellular organelles accumulated in FYCO1 (c.2206C>T) KI lens-like organoid structures and in fyco1 −/− mice lenses. In summary, our data confirm the loss of FYCO1 function results in a diminished autophagic flux, impaired organelle removal, and cataractogenesis. Abbreviations: CC: congenital cataracts; DE: differentially expressed; ER: endoplasmic reticulum; FYCO1: FYVE and coiled-coil domain containing 1; hESC: human embryonic stem cell; KI: knock-in; OFZ: organelle-free zone; qRT-PCR: quantitative real-time PCR; PE: phosphatidylethanolamine; RNA-Seq: RNA sequencing; SD: standard deviation; sgRNA: single guide RNA; shRNA: shorthairpin RNA; TEM: transmission electron microscopy; WT: wild type
Publisher: United States: Taylor & Francis
Language: English
Identifier: ISSN: 1554-8627
EISSN: 1554-8635
DOI: 10.1080/15548627.2022.2025570
PMID: 35343376
Source: MEDLINE
PubMed Central

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The role of FYCO1-dependent autophagy in lens fiber cell differentiation

2022 Informa UK Limited, trading as Taylor & Francis Group 2022 ;2022 Informa UK Limited, trading as Taylor & Francis Group 2022 Informa UK Limited, trading as Taylor & Francis Group ;ISSN: 1554-8627 ;EISSN: 1554-8635 ;DOI: 10.1080/15548627.2022.2025570 ;PMID: 35343376

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