Nuclear N-Glycosylation Redefines the Glycoscape and Directs Cell Identity
Li, F.; Wu, X.; Xie, Y.; Yang, J.; Xi, J.; Sun, Y.; Chen, J.; Wu, X.; Huang, S.; Zhang, C.; Zheng, Y.; Li, W.; Zuo, X.; Li, Y.; Chen, K.; Lai, X.; Liu, X.; Zhong, W.; Zeng, J.; Wu, Q.; Garcia, B.; Lu, H.; Xia, H.; Zhou, W.; Zhang, Y.
Show abstract
Glycans modify nucleic acids, proteins and lipids in fundamental biological processes, but have long been considered confined to the secretory pathway and cell surface. Here, we challenge this view with evidence that N-glycosylation, a ubiquitous glycan modification, occurs within cell nuclei across tissues and species, exhibiting cell type-dependent abundance and localization patterns. Using a multi-faceted approach, we show that numerous classical membrane and secreted glycoproteins localize to the nucleus with N-glycan modifications, exemplified by the cell adhesion molecule L1CAM. Mechanistically, we show that the N-glycosylated L1CAM is transported to the nucleus by KPNB1, where it transcriptionally modulates neuronal differentiation. Moreover, this nuclear N-glycosylation event contributes to neurodevelopmental disorders and is pharmacologically reversible. These findings revise the cellular geography of N-glycosylation and expand the known routes of protein trafficking, and highlight nuclear N-glycosylation pathways as potential therapeutic entry points for developmental disorders.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CRISPR screens and lectin microarrays identify novel high mannose N-glycan regulators 95%
- Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5 95%
- Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation 95%
Similar papers in this journal
- Cell-Type Resolved Protein Atlas of Brain Lysosomes Identifies SLC45A1-Associated Disease as a Lysosomal Disorder 95%
- Lysine vitcylation is a novel vitamin C-derived protein modification that enhances STAT1-mediated immune response 94%
- A conserved fertilization complex of Izumo1, Spaca6, and Tmem81 mediates sperm-egg interaction in vertebrates 93%
Similar papers in this journal
- PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape 94%
- Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control 94%
- RNF13 mediates pH- and Ca2+-dependent regulation of lysosomal positioning 93%
Similar papers in this journal
- C-terminal tagging, transmembrane domain hydrophobicity, and an ER retention motif influence the secretory trafficking of the inner nuclear membrane protein emerin 94%
- The ORP9-ORP11 dimer promotes sphingomyelin synthesis 94%
- Stratification of enterochromaffin cells by single-cell expression analysis 94%
Similar papers in this journal
- Human-specific features and developmental dynamics of the brain N-glycome 95%
- Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma 94%
- Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.