Man2C1, an α-mannosidase, is involved in the trimming of free oligosaccharides in the cytosol

Tadashi Suzuki*, Izumi Hara, Miyako Nakano, Masaki Shigeta, Takatoshi Nakagawa, Akihiro Kondo, Yoko Funakoshi, Naoyuki Taniguchi

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The endoplasmic-reticulum-associated degradation of misfolded (glyco)proteins ensures that only functional, correctly folded proteins exit from the endoplasmic reticulum and that misfolded ones are degraded by the ubiquitin-proteasome system. During the degradation of misfolded glycoproteins, they are deglycosylated by the PNGase (peptide:N-glycanase). The free oligosaccharides released by PNGase are known to be further catabolized by a cytosolic α-mannosidase, although the gene encoding this enzyme has not been identified unequivocally. The findings in the present study demonstrate that an α-mannosidase, Man2C1, is involved in the processing of free oligosaccharides that are formed in the cytosol. When the human Man2C1 orthologue was expressed in HEK-293 cells, most of the enzyme was localized in the cytosol. Its activity was enhanced by Co 2+, typical of other known cytosolic α-mannosidases so far characterized from animal cells. The down-regulation of Man2C1 activity by a small interfering RNA drastically changed the amount and structure of oligosaccharides accumulating in the cytosol, demonstrating that Man2C1 indeed is involved in free oligosaccharide processing in the cytosol. The oligosaccharide processing in the cytosol by PNGase, endo-β-N-acetylglucosaminidase and α-mannosidase may represent the common 'non-lysosomal' catabolic pathway for N-glycans in animal cells, although the molecular mechanism as well as the functional importance of such processes remains to be determined.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalBiochemical Journal
Volume400
Issue number1
DOIs
Publication statusPublished - 15 Nov 2006

Keywords

  • α-mannosidase
  • Cytosol
  • Free oligosaccharide
  • N-glycan
  • Non-lysosomal degradation
  • Peptide:N-glycanase (PNGase)

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    Suzuki, T., Hara, I., Nakano, M., Shigeta, M., Nakagawa, T., Kondo, A., ... Taniguchi, N. (2006). Man2C1, an α-mannosidase, is involved in the trimming of free oligosaccharides in the cytosol. Biochemical Journal, 400(1), 33-41. https://doi.org/10.1042/BJ20060945