Identification and characterization of UDP-mannose in human cell lines and mouse organs: Differential distribution across brain regions and organs

  • Biochem Biophys Res Commun. 2018 Jan 1;495(1):401-407. doi: 10.1016/j.bbrc.2017.10.173.
Kazuki Nakajima  1 Yasuhiko Kizuka  2 Yoshiki Yamaguchi  3 Yoshio Hirabayashi  4 Kazuo Takahashi  5 Yukio Yuzawa  5 Naoyuki Taniguchi  6
Affiliations
  • 1. Department of Academic Research Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 2. Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 3. Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 4. Molecular Membrane Neuroscience, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 5. Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
  • 6. Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: [email protected].
Abstract

Mannosylation in the endoplasmic reticulum is a key process for synthesizing various glycans. Guanosine diphosphate mannose (GDP-Man) and dolichol phosphate-mannose serve as donor substrates for mannosylation in mammals and are used in N-glycosylation, O-mannosylation, C-mannosylation, and the synthesis of glycosylphosphatidylinositol-anchor (GPI-anchor). Here, we report for the first time that low-abundant uridine diphosphate-mannose (UDP-Man), which can serve as potential donor substrate, exists in mammals. Liquid chromatography-mass spectrometry (LC-MS) analyses showed that mouse brain, especially hypothalamus and neocortex, contains higher concentrations of UDP-Man compared to Other organs. In cultured human cell lines, addition of mannose in media increased UDP-Man concentrations in a dose-dependent manner. These findings indicate that in mammals the minor nucleotide sugar UDP-Man regulates glycosylation, especially mannosylation in specific organs or conditions.

Keywords
Hypothalamus; LC-ESI-MS/MS; Mannosylation; Neocortex; Nucleotide sugar; UDP-mannose.
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