PXD017001 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The indispensable role of autophagy in lens morphogenesis |
Description | FYVE and coiled-coil domain containing 1 (FYCO1) is expressed ubiquitously and is required for microtubule-dependent, plus-end-directed transport of autophagic vesicles. We previously reported the loss of function mutations in FYCO1 responsible for cataractogenesis with no other ocular and/or extra-ocular phenotype. Here, we show that Fyco1-/- lenses recapitulated the cataract phenotype and exhibited diminished autophagy, consistent with a critical role of Fyco1 and autophagy in lens morphogenesis. Transcriptome coupled with proteome and metabolome profiling identified many differentially expressed, autophagy-related, genes, proteins, and lipids, respectively in Fyco1-/- lenses. Flow cytometry of FYCO1 (c.2206C>T) knock-in (KI) human lens epithelial (HLE) cell line confirmed reduced amounts of membrane-bound LC3B-II and autophagic vesicles resulting from the loss of FYCO1. Transmission electron microscopy showed persistent organelle mass in Fyco1-/- lenses and FYCO1 KI lens-like organoid structures, which were further confirmed through western blot analysis. In summary, our data show that the absence of FYCO1 causes diminished autophagy, delayed organelle degradation, and cataractogenesis. These data support the model of FYCO1 supplementing basal autophagy in the lens to meet the physiological necessity of high autophagy levels required during lens fiber cell differentiation and lack thereof results in delayed organelle removal. |
HostingRepository | PRIDE |
AnnounceDate | 2023-05-10 |
AnnouncementXML | Submission_2023-05-10_08:57:39.447.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | OMGenetics |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-01-08 00:21:13 | ID requested | |
⏵ 1 | 2023-05-10 08:57:40 | announced | |
2 | 2023-11-14 08:45:58 | announced | 2023-11-14: Updated project metadata. |
Publication List
Khan SY, Ali M, Kabir F, Na CH, Delannoy M, Ma Y, Qiu C, Costello MJ, Hejtmancik JF, Riazuddin SA, The role of FYCO1-dependent autophagy in lens fiber cell differentiation. Autophagy, 18(9):2198-2215(2022) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: Mass-spectrometry,H9 hESC-derived Lentoid Bodies, TMT, Proteome |
Contact List
S. AmerRiazuddin |
contact affiliation | The Wilmer Eye Institute, Johns Hopkins University Schoolof Medicine, Baltimore, Maryland 21287 USA |
contact email | riazuddin@jhmi.edu |
lab head | |
OMGenetics |
contact affiliation | Johns Hopkins Wilmer Eye Institute |
contact email | omgenetics@jhmi.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017001
- Label: PRIDE project
- Name: The indispensable role of autophagy in lens morphogenesis