PXD018624 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The Batten disease gene product CLN3 is required for the efflux of glycerophosphodiesters from lysosomes |
Description | The lysosome has many cellular roles, including degrading and recycling macromolecules and signaling to the mTORC1 growth regulator. Lysosomal dysfunction occurs in various human diseases, including common neurodegenerative diseases as well as monogenic lysosomal storage disorders (LSDs). For most LSDs the causal genes have been identified, but in many cases the function of the implicated gene is unknown. Here, we develop the LysoTag mouse line for the tissue-specific isolation of intact lysosomes that are compatible with the multimodal profiling of their contents. We apply it to the study of CLN3, a lysosomal transmembrane protein of unclear function whose loss causes juvenile neuronal ceroid lipofuscinosis (Batten disease), a lethal neurodegenerative LSD. Untargeted metabolite profiling of lysosomes from the brains of mice lacking CLN3 revealed a massive accumulation of glycerophosphodiesters (GPDs), the end products of glycerophospholipid catabolism. GPDs also accumulate in the lysosomes of CLN3-deficient cultured cells and stable isotope tracing experiments show that CLN3 is required for their lysosomal egress. Loss of CLN3 also alters upstream glycerophospholipid catabolism in the lysosome. Our results suggest that CLN3 is a lysosomal effluxer of GPDs and reveal Batten disease as the first, to our knowledge, neurodegenerative LSD with a primary defect in glycerophospholipid metabolism. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:38:15.268.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alessandro Ori |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-04-17 05:33:35 | ID requested | |
1 | 2022-07-11 03:03:50 | announced | |
⏵ 2 | 2024-10-22 05:38:16 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1038/s41586-022-05221-y; |
Laqtom NN, Dong W, Medoh UN, Cangelosi AL, Dharamdasani V, Chan SH, Kunchok T, Lewis CA, Heinze I, Tang R, Grimm C, Dang Do AN, Porter FD, Ori A, Sabatini DM, Abu-Remaileh M, CLN3 is required for the clearance of glycerophosphodiesters from lysosomes. Nature, 609(7929):1005-1011(2022) [pubmed] |
Keyword List
submitter keyword: Batten disease, liver, mouse, CLN3,lysosome |
Contact List
Alessandro Ori |
contact affiliation | Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) Beutenbergstrasse 11 07745 Jena, Germany |
contact email | alessandro.ori@leibniz-fli.de |
lab head | |
Alessandro Ori |
contact affiliation | Leibniz Institute on Aging |
contact email | aleori@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018624
- Label: PRIDE project
- Name: The Batten disease gene product CLN3 is required for the efflux of glycerophosphodiesters from lysosomes