PXD015429-1

PXD015429 is an original dataset announced via ProteomeXchange.

Title	Galnt11 differential tissue glycoproteomics
Description	Chronic kidney disease (CKD) affects more than 20 million Americans and approximately 10% of the population worldwide, and thus represents a major public health concern. Genome-wide association studies (GWAS) of kidney functional decline have identified genes associated with CKD, but the precise roles and mechanisms by which they influence kidney function remained largely unexplored. Here, we examine the role of one GWAS identified gene by creating mice deficient for Galnt11, which encodes a member of the enzyme family that initiates protein Oglycosylation, an essential post-translational modification known to influence protein function and stability. We find that Galnt11-deficient mice display low molecular weight proteinuria and have specific defects in proximal tubule-mediated resorption of vitamin D binding protein, a1-microglobulin and retinol binding protein. Moreover, we identify the endocytic receptor megalin (LRP2) as a direct target of Galnt11 in vivo. Megalin in Galnt11-deficient mice displays reduced ligand binding and undergoes age-related loss within the kidney. Differential mass spectrometry revealed specific sites of Galnt11-mediated glycosylation within mouse kidney megalin/LRP2 that are known to be involved in ligand binding, suggesting that Oglycosylation directly influences the ability to bind ligands. In support of this, recombinant megalin containing these sites displayed reduced albumin binding in cells deficient for Galnt11. Our results provide insight into the association between GALNT11 and CKD, and identify a role for Galnt11 in proper kidney function.
HostingRepository	PRIDE
AnnounceDate	2019-11-04
AnnouncementXML	Submission_2019-11-04_05:56:22.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katrine Schjoldager
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-12 06:21:44	ID requested
⏵ 1	2019-11-04 05:56:23	announced
2	2019-11-25 00:43:32	announced	2019-11-25: Updated publication reference for PubMed record(s): 31740596.
3	2024-10-22 04:57:34	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Mouse Brain, Kidney, Liver

Katrine Schjoldager
contact affiliation	University of Copenhagen, Copenhagen Center for Glycomics
contact email	schjoldager@sund.ku.dk
lab head
Katrine Schjoldager
contact affiliation	University of Copenhagen
contact email	schjoldager@sund.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015429
     1. Label: PRIDE project
     2. Name: Galnt11 differential tissue glycoproteomics