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

Author

Listed:
  • Mathias I. Nielsen

    (University of Copenhagen)

  • Noortje Haan

    (University of Copenhagen)

  • Weston Kightlinger

    (University of Copenhagen
    Northwestern University)

  • Zilu Ye

    (University of Copenhagen
    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)

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.

Suggested Citation

  • Mathias I. Nielsen & Noortje Haan & Weston Kightlinger & Zilu Ye & Sally Dabelsteen & Minyan Li & Michael C. Jewett & Ieva Bagdonaite & Sergey Y. Vakhrushev & Hans H. Wandall, 2022. "Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33806-8
    DOI: 10.1038/s41467-022-33806-8
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    References listed on IDEAS

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    1. Tanya M. Teslovich & Kiran Musunuru & Albert V. Smith & Andrew C. Edmondson & Ioannis M. Stylianou & Masahiro Koseki & James P. Pirruccello & Samuli Ripatti & Daniel I. Chasman & Cristen J. Willer & C, 2010. "Biological, clinical and population relevance of 95 loci for blood lipids," Nature, Nature, vol. 466(7307), pages 707-713, August.
    2. Stacy A. Malaker & Nicholas M. Riley & D. Judy Shon & Kayvon Pedram & Venkatesh Krishnan & Oliver Dorigo & Carolyn R. Bertozzi, 2022. "Revealing the human mucinome," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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