Adaptive regulation at the cell surface by N-glycosylation
- PMID: 19761541
- DOI: 10.1111/j.1600-0854.2009.00981.x
Adaptive regulation at the cell surface by N-glycosylation
Abstract
The association of receptors and solute transporters with components of the endocytic machinery regulates their surface levels, and thereby cellular sensitivity to cytokines, ligands and nutrients in the extracellular environment. Most transmembrane receptors and solute transporters are glycoproteins, and the Asn (N)-linked oligosaccharides (N-glycans) can bind animal lectins, forming multivalent lattices or microdomains that regulate glycoprotein mobility in the plane of membrane. The N-glycan number (sequence-encoded NXS/T) and context-dependent Golgi N-glycan branching cooperate to regulate glycoprotein affinities for the galectin family of lectins. Galectin-3 binding reduces EGF receptor trafficking into clathrin-coated pits and caveolae lipid rafts, decreases ligand-independent receptor activation and promotes alpha5beta1 integrin remodelling in focal adhesions. N-glycan branching in the medial Golgi increases glycan affinity for galectins, and the Golgi pathway is sensitive to uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) supply, in turn hexosamine pathway metabolites (fructose-6-P, glutamine and acetyl-CoA). Thus, lattice avidity and cellular responsiveness to extracellular cues are regulated in an adaptive manner by metabolism and Golgi modification to glycoproteins. Computational modelling of the hexosamine/Golgi/lattice has provided new insight on cell surface adaptation in cancer and autoimmune disease.
Similar articles
-
Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation.Cell. 2007 Apr 6;129(1):123-34. doi: 10.1016/j.cell.2007.01.049. Cell. 2007. PMID: 17418791
-
Manipulating cell surface glycoproteins by targeting N-glycan-galectin interactions.Methods Enzymol. 2010;480:245-66. doi: 10.1016/S0076-6879(10)80012-6. Methods Enzymol. 2010. PMID: 20816213 Review.
-
Glycosylation, galectins and cellular signaling.Curr Opin Cell Biol. 2011 Aug;23(4):383-92. doi: 10.1016/j.ceb.2011.05.001. Epub 2011 May 26. Curr Opin Cell Biol. 2011. PMID: 21616652 Review.
-
N-Glycans in cancer progression.Glycobiology. 2008 Oct;18(10):750-60. doi: 10.1093/glycob/cwn071. Epub 2008 Aug 13. Glycobiology. 2008. PMID: 18701722 Review.
-
The galectin lattice at a glance.J Cell Sci. 2015 Jul 1;128(13):2213-9. doi: 10.1242/jcs.151159. Epub 2015 Jun 19. J Cell Sci. 2015. PMID: 26092931 Review.
Cited by
-
Genetics of glycosylation in mammalian development and disease.Nat Rev Genet. 2024 May 9. doi: 10.1038/s41576-024-00725-x. Online ahead of print. Nat Rev Genet. 2024. PMID: 38724711 Review.
-
Galectin-3 impairs calcium transients and β-cell function.Nat Commun. 2024 May 1;15(1):3682. doi: 10.1038/s41467-024-47959-1. Nat Commun. 2024. PMID: 38693121 Free PMC article.
-
Human brain glycoform coregulation network and glycan modification alterations in Alzheimer's disease.Sci Adv. 2024 Apr 5;10(14):eadk6911. doi: 10.1126/sciadv.adk6911. Epub 2024 Apr 5. Sci Adv. 2024. PMID: 38579000 Free PMC article.
-
Impacts of β-1, 3-N-acetylglucosaminyltransferases (B3GNTs) in human diseases.Mol Biol Rep. 2024 Mar 29;51(1):476. doi: 10.1007/s11033-024-09405-9. Mol Biol Rep. 2024. PMID: 38553573 Review.
-
The role of N-glycosylation in cancer.Acta Pharm Sin B. 2024 Mar;14(3):1098-1110. doi: 10.1016/j.apsb.2023.10.014. Epub 2023 Oct 27. Acta Pharm Sin B. 2024. PMID: 38486989 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources