PXD031582-2

PXD031582 is an original dataset announced via ProteomeXchange.

Title	LOSS OF THE BATTEN DISEASE PROTEIN CLN3 LEADS TO MIS-TRAFFICKING OF M6PR AND DEFECTIVE AUTOPHAGIC-LYSOSOMAL REFORMATION
Description	Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. Conversely, CLN3 overexpression promotes the formation of multiple lysosomal tubules, which are autophagy and CI-M6PR-dependent, generating newly formed proto-lysosomes. Together, our findings reveal that CLN3 functions as a link between the M6P-dependent trafficking of lysosomal enzymes and lysosomal reformation pathway, explaining the global impairment of lysosomal function in Batten disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:49:13.420.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessia Calcagnì
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-10 14:57:30	ID requested
1	2023-06-20 14:44:52	announced
⏵ 2	2024-10-22 05:49:13	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human,CLN3,Batten,lysosome

Andrea Ballabio
contact affiliation	Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy. Department of Translational Medicine, University of Naples "Federico II", Italy. Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Houston, TX, USA.
contact email	ballabio@tigem.it
lab head
Alessia Calcagnì
contact affiliation	1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 2. Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA
contact email	alessia.calcagni@bcm.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD031582

PRIDE project URI

• PRIDE
  1. PXD031582
     1. Label: PRIDE project
     2. Name: LOSS OF THE BATTEN DISEASE PROTEIN CLN3 LEADS TO MIS-TRAFFICKING OF M6PR AND DEFECTIVE AUTOPHAGIC-LYSOSOMAL REFORMATION