PXD018624-2

PXD018624 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: Batten disease, liver, mouse, CLN3,lysosome

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

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PRIDE project URI

• PRIDE
  1. PXD018624
     1. Label: PRIDE project
     2. Name: The Batten disease gene product CLN3 is required for the efflux of glycerophosphodiesters from lysosomes