The relative contribution of mannose salvage pathways to glycosylation in PMI-deficient mouse embryonic fibroblast cells

The FEBS Journal
Naonobu FujitaAtsushi Nishikawa

Abstract

Mannose for mammalian glycan biosynthesis can be imported directly from the medium, derived from glucose or salvaged from endogenous or external glycans. All pathways must generate mannose 6-phosphate, the activated form of mannose. Imported or salvaged mannose is directly phosphorylated by hexokinase, whereas fructose 6-phosphate from glucose is converted to mannose 6-phosphate by phosphomannose isomerase (PMI). Normally, PMI provides the majority of mannose for glycan synthesis. To assess the contribution of PMI-independent pathways, we used PMI-null fibroblasts to study N-glycosylation of DNase I, a highly sensitive indicator protein. In PMI-null cells, imported mannose and salvaged mannose make a significant contribution to N-glycosylation. When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated. Adding approximately 13 microm mannose to the medium completely restored normal glycosylation. Treatment with bafilomycin A(1), an inhibitor of lysosomal acidification, also markedly reduced N-glycosylation of DNase I, but in this case only 8 microm mannose was required to restore full glycosylati...Continue Reading

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Citations

Jun 5, 2010·The Journal of Membrane Biology·Mecedes Cano, Anunciación A Ilundain
Mar 19, 2014·International Journal of Molecular Sciences·Philip M JedrzejewskiCleo Kontoravdi
Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yoichiro HaradaTadashi Suzuki
Aug 25, 2009·Human Mutation·Wendy VleugelsThierry Hennet
Feb 7, 2012·American Journal of Human Genetics·Melanie A JonesMadhuri R Hegde
Feb 11, 2014·Protein Science : a Publication of the Protein Society·Annamarie C Dalton, William A Barton
Dec 11, 2019·The Journal of Biological Chemistry·Alex BroussardMichael Boyce
Apr 9, 2020·Journal of Inherited Metabolic Disease·Anna ČechováTomáš Honzík
Jul 17, 2009·The Journal of Nutrition·Satish C Kalhan
Oct 25, 2020·Journal of Inherited Metabolic Disease·Muriel GirardPascale De Lonlay

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