Metabolic homeostasis and tissue renewal are dependent on beta1,6GlcNAc-branched N-glycans.

Abstract

Golgi beta1,6-N-acetylglucosaminyltransferase V (Mgat5) produces beta1,6GlcNAc-branched N-glycans on glycoproteins, which increases their affinity for galectins and opposes loss from the cell surface to constitutive endocytosis. Oncogenic transformation increases Mgat5 expression, increases beta1,6GlcNAc-branched N-glycans on epidermal growth factor and transforming growth factor-beta receptors, and enhances sensitivities to ligands, cell motility, and tumor metastasis. Here, we demonstrate that Mgat5(-/-) mouse embryonic fibroblasts (MEFs) display reduced sensitivity to anabolic cytokines and reduced glucose uptake and proliferation. Mgat5(-/-) mice are also hypoglycemic, resistant to weight gain on a calorie-enriched diet, hypersensitive to fasting, and display increased oxidative respiration and reduced fecundity. Serum-dependent activation of the extracellular response kinase (growth) and Smad2/3 (arrest) pathways in Mgat5(-/-) MEFs and bone marrow cells reveals an imbalance favoring arrest. Mgat5(-/-) mice have fewer muscle satellite cells, less osteogenic activity in bone marrow, and accelerated loss of muscle and bone mass with aging. Our results suggest that beta1,6GlcNAc-branched N-glycans promote sensitivity to anabolic cytokines, and increase fat stores, tissue renewal, and longevity.

• Authors: Pam Cheung, Judy Pawling, Emily A Partridge, Balram Sukhu, Marc Grynpas, James W Dennis
• Journal: Glycobiology (Glycobiology) Vol. 17 Issue 8 Pg. 828-37 (Aug 2007) ISSN: 0959-6658 [Print] England
• PMID: 17483135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Polysaccharides
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
• Glucose

Topics

• Animals
• Bone Marrow Cells (metabolism)
• Cells, Cultured
• Glucose (metabolism)
• Glycoproteins (metabolism)
• Glycosylation
• Homeostasis
• Mice
• Mice, Inbred C57BL
• Mice, Inbred Strains
• Molecular Sequence Data
• N-Acetylglucosaminyltransferases (chemistry, metabolism)
• Polysaccharides (metabolism)
• Time Factors