Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation.

Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, Demetriou M, Dennis JW
Cell. 2007 129 (1): 123-34

PMID: 17418791 · DOI:10.1016/j.cell.2007.01.049

The number of N-glycans (n) is a distinct feature of each glycoprotein sequence and cooperates with the physical properties of the Golgi N-glycan-branching pathway to regulate surface glycoprotein levels. The Golgi pathway is ultrasensitive to hexosamine flux for the production of tri- and tetra-antennary N-glycans, which bind to galectins and form a molecular lattice that opposes glycoprotein endocytosis. Glycoproteins with few N-glycans (e.g., TbetaR, CTLA-4, and GLUT4) exhibit enhanced cell-surface expression with switch-like responses to increasing hexosamine concentration, whereas glycoproteins with high numbers of N-glycans (e.g., EGFR, IGFR, FGFR, and PDGFR) exhibit hyperbolic responses. Computational and experimental data reveal that these features allow nutrient flux stimulated by growth-promoting high-n receptors to drive arrest/differentiation programs by increasing surface levels of low-n glycoproteins. We have identified a mechanism for metabolic regulation of cellular transition between growth and arrest in mammals arising from apparent coevolution of N-glycan number and branching.

MeSH Terms (22)

Animals Antigens, CD Antigens, Differentiation Cell Differentiation Cell Line Cell Line, Tumor Cell Proliferation CTLA-4 Antigen Endocytosis Glycoproteins Glycosylation Golgi Apparatus Hexosamines Humans Kinetics Mice Mice, Transgenic Models, Biological Polysaccharides Receptor Protein-Tyrosine Kinases T-Lymphocytes Uridine Diphosphate N-Acetylglucosamine

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