PXD027616-2

PXD027616 is an original dataset announced via ProteomeXchange.

Title	Discovery of a pathway for endogenous mucin glycodomain catabolism in mammals
Description	Mucins are functionally implicated in a range of human pathologies, including cystic fibrosis, influenza, bacterial endocarditis, gut dysbiosis, and cancer. These observations have motivated the study of mucin biosynthesis as well as development of strategies for inhibition of mucin glycosylation. Mammalian pathways for mucin catabolism, however, have remained underexplored. The canonical view, derived from analysis of N-glycoconjugates in human lysosomal storage disorders, is that proteolysis and glycan degradation occur largely independently. Here, we challenge this view by providing genetic and biochemical evidence supporting mammalian proteolysis of heavily O-glycosylated mucin domains, without prior deglycosylation. Using activity screening coupled with mass spectrometry we ascribed mucin-degrading activity in murine liver to the lysosomal protease cathepsin D. Knockout of cathepsin D in a murine model of the human lysosomal storage disorder neuronal ceroid lipofuscinosis resulted in accumulation of mucins in liver-resident macrophages. Our findings suggest that mucin-degrading activity is not limited to the bacterial kingdom and is a component of glycoprotein catabolism in mammalian tissues.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:21.713.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicholas Riley
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-28 02:30:27	ID requested
1	2022-09-03 00:29:40	announced
⏵ 2	2023-11-14 08:53:22	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, Catabolism, Glycoproteomics, Mucins, Mucinase

Carolyn Bertozzi
contact affiliation	Stanford University, Department of Chemistry and ChEM-H, Stanford, CA Howard Hughes Medical Institute, Stanford, CA
contact email	bertozzi@stanford.edu
lab head
Nicholas Riley
contact affiliation	Stanford University
contact email	riley.nicholasm@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027616
     1. Label: PRIDE project
     2. Name: Discovery of a pathway for endogenous mucin glycodomain catabolism in mammals