Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Galnt11 regulates kidney function by glycosylating the endocytosis receptor megalin to modulate ligand binding

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Adolescents' perceptions of family social status correlate with health and life chances: A twin difference longitudinal cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Dynamic coupling of whole-brain neuronal and neurotransmitter systems

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Unfolding of monomeric lipoprotein lipase by ANGPTL4: Insight into the regulation of plasma triglyceride metabolism

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. N-acyl taurines are endogenous lipid messengers that improve glucose homeostasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Early sarcomere and metabolic defects in a zebrafish pitx2c cardiac arrhythmia model

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Apolipoprotein M and risk of type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Effect of insulin on natriuretic peptide gene expression in porcine heart

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Aging suppresses sphingosine-1-phosphate chaperone ApoM in circulation resulting in maladaptive organ repair

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Reduced apolipoprotein M and adverse outcomes across the spectrum of human heart failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  • E Tian
  • Shengjun Wang
  • Liping Zhang
  • Ying Zhang
  • May C Malicdan
  • Yang Mao
  • Christina Christoffersen
  • Lawrence A Tabak
  • Katrine T Schjoldager
  • Kelly G Ten Hagen
View graph of relations

Chronic kidney disease (CKD) affects more than 20 million Americans and ∼10% of the population worldwide. Genome-wide association studies (GWAS) of kidney functional decline have identified genes associated with CKD, but the precise mechanisms by which they influence kidney function remained largely unexplored. Here, we examine the role of 1 GWAS-identified gene by creating mice deficient for Galnt11, which encodes a member of the enzyme family that initiates protein O-glycosylation, an essential posttranslational 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, α1-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 O-glycosylation 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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number50
Pages (from-to)25196-25202
Number of pages7
ISSN0027-8424
DOIs
Publication statusPublished - 10 Dec 2019

ID: 58645819