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 language | English (US) |
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Pages (from-to) | 2-16 |
Number of pages | 15 |
Journal | Journal of molecular cell biology |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - 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