Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast

Hiroto Hirayama, Tsugiyo Matsuda, Yae Tsuchiya, Ritsuko Oka, Junichi Seino, Chengcheng Huang, Kazuki Nakajima, Yoichi Noda, Yuichi Shichino, Shintaro Iwasaki, Tadashi Suzuki

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Abstract

In eukaryotic cells, unconjugated oligosaccharides that are structurally related to N-glycans (i.e. free N-glycans) are generated either from misfolded N-glycoproteins destined for the endoplasmic reticulum-associated degradation or from lipid-linked oligosaccharides, donor substrates for N-glycosylation of proteins. The mechanism responsible for the generation of free N-glycans is now well-understood, but the issue of whether other types of free glycans are present remains unclear. Here, we report on the accumulation of free, O-mannosylated glycans in budding yeast that were cultured in medium containing mannose as the carbon source. A structural analysis of these glycans revealed that their structures are identical to those of O-mannosyl glycans that are attached to glycoproteins. Deletion of the cyc8 gene, which encodes for a general transcription repressor, resulted in the accumulation of excessive amounts of free O-glycans, concomitant with a severe growth defect, a reduction in the level of an O-mannosylated protein, and compromised cell wall integrity. Our findings provide evidence in support of a regulated pathway for the degradation of O-glycoproteins in yeast and offer critical insights into the catabolic mechanisms that control the fate of O-glycosylated proteins.

Original languageEnglish
Pages (from-to)15900-15911
Number of pages12
JournalJournal of Biological Chemistry
Volume294
Issue number44
DOIs
Publication statusPublished - 01-11-2019

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hirayama, H., Matsuda, T., Tsuchiya, Y., Oka, R., Seino, J., Huang, C., Nakajima, K., Noda, Y., Shichino, Y., Iwasaki, S., & Suzuki, T. (2019). Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast. Journal of Biological Chemistry, 294(44), 15900-15911. https://doi.org/10.1074/jbc.RA119.009491