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J Mol Cell Biol. 2016 Feb;8(1):2-16. doi: 10.1093/jmcb/mjv033. Epub 2015 Jun 1.

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

Author information

1
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
2
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
3
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
4
Department of Biological Chemistry, Johns Hopkins University Medical School, Baltimore, MD 21205, USA.
5
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada dvocadlo@sfu.ca.

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. We show that loss of O-GlcNAc, induced by either inhibition of O-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.

KEYWORDS:

O-GlcNAcylation; glycosylation; nuclear pore complex; nucleoporin; post-translational modification; protein stability; ubiquitination

PMID:
26031751
PMCID:
PMC4710208
DOI:
10.1093/jmcb/mjv033
[Indexed for MEDLINE]
Free PMC Article

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