Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line

Mathias I. Nielsen, Noortje Haan, Weston Kightlinger, Zilu Ye, Sally Dabelsteen, Minyan Li, Michael C. Jewett, Ieva Bagdonaite, Sergey Y. Vakhrushev () and Hans H. Wandall ()
Additional contact information
Mathias I. Nielsen: University of Copenhagen
Noortje Haan: University of Copenhagen
Weston Kightlinger: University of Copenhagen
Zilu Ye: University of Copenhagen
Sally Dabelsteen: University of Copenhagen
Minyan Li: University of Copenhagen
Michael C. Jewett: Northwestern University
Ieva Bagdonaite: University of Copenhagen
Sergey Y. Vakhrushev: University of Copenhagen
Hans H. Wandall: University of Copenhagen

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Mucin-type-O-glycosylation on proteins is integrally involved in human health and disease and is coordinated by an enzyme family of 20 N-acetylgalactosaminyltransferases (GalNAc-Ts). Detailed knowledge on the biological effects of site-specific O-glycosylation is limited due to lack of information on specific glycosylation enzyme activities and O-glycosylation site-occupancies. Here we present a systematic analysis of the isoform-specific targets of all GalNAc-Ts expressed within a tissue-forming human skin cell line, and demonstrate biologically significant effects of O-glycan initiation on epithelial formation. We find over 300 unique glycosylation sites across a diverse set of proteins specifically regulated by one of the GalNAc-T isoforms, consistent with their impact on the tissue phenotypes. Notably, we discover a high variability in the O-glycosylation site-occupancy of 70 glycosylated regions of secreted proteins. These findings revisit the relevance of individual O-glycosylation sites in the proteome, and provide an approach to establish which sites drive biological functions.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33806-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33806-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33806-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().