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Glycobiology. 2007 Aug;17(8):828-37. Epub 2007 May 4.

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

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Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue R988, Toronto, ON, Canada M5G 1X5.


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.

[Indexed for MEDLINE]

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