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PXD018624 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Batten disease gene product CLN3 is required for the efflux of glycerophosphodiesters from lysosomes
DescriptionThe 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlessandro Ori
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-17 05:33:35ID requested
12022-07-11 03:03:50announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: lysosome, mouse, liver, Batten disease, CLN3
Contact List
Alessandro Ori
contact affiliationLeibniz Institute on Aging – Fritz Lipmann Institute (FLI) Beutenbergstrasse 11 07745 Jena, Germany
contact emailalessandro.ori@leibniz-fli.de
lab head
Alessandro Ori
contact affiliationLeibniz Institute on Aging
contact emailaleori@gmail.com
dataset submitter
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