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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Glycoproteins
  • Hexosamines
  • Polysaccharides
  • Uridine Diphosphate N-Acetylglucosamine
  • Receptor Protein-Tyrosine Kinases