Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter

Yanping Zhu, Ta Wei Liu, Zarina Madden, Scott A. Yuzwa, Kelsey Murray, Samy Cecioni, Natasha Zachara, David J. Vocadlo

Research output: Contribution to journalArticlepeer-review

Abstract

O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. Many nucleoporins (Nups) comprising the NPC are constitutively O-GlcNAcylated, but the functional role of this modification remains enigmatic. Weshowthat loss ofO-GlcNAc, induced by either inhibition ofO-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans.

Original languageEnglish (US)
Pages (from-to)2-16
Number of pages15
JournalJournal of molecular cell biology
Volume8
Issue number1
DOIs
StatePublished - Feb 2016

Keywords

  • Glycosylation
  • Nuclear pore complex
  • Nucleoporin
  • O-GlcNAcylation
  • Post-translational modification
  • Protein stability
  • Ubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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