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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 - 01-01-2019

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Yeast
Polysaccharides
Glycoproteins
Yeasts
Degradation
Endoplasmic Reticulum-Associated Degradation
Glycosylation
Proteins
Saccharomycetales
Gene Deletion
Eukaryotic Cells
Transcription
Mannose
Oligosaccharides
Structural analysis
Cell Wall
Carbon
Genes
Cells
Defects

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hirayama, Hiroto ; Matsuda, Tsugiyo ; Tsuchiya, Yae ; Oka, Ritsuko ; Seino, Junichi ; Huang, Chengcheng ; Nakajima, Kazuki ; Noda, Yoichi ; Shichino, Yuichi ; Iwasaki, Shintaro ; Suzuki, Tadashi. / Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast. In: Journal of Biological Chemistry. 2019 ; Vol. 294, No. 44. pp. 15900-15911.
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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, vol. 294, no. 44, pp. 15900-15911. https://doi.org/10.1074/jbc.RA119.009491

Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast. / Hirayama, Hiroto; Matsuda, Tsugiyo; Tsuchiya, Yae; Oka, Ritsuko; Seino, Junichi; Huang, Chengcheng; Nakajima, Kazuki; Noda, Yoichi; Shichino, Yuichi; Iwasaki, Shintaro; Suzuki, Tadashi.

In: Journal of Biological Chemistry, Vol. 294, No. 44, 01.01.2019, p. 15900-15911.

Research output: Contribution to journalArticle

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T1 - Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast

AU - Hirayama, Hiroto

AU - Matsuda, Tsugiyo

AU - Tsuchiya, Yae

AU - Oka, Ritsuko

AU - Seino, Junichi

AU - Huang, Chengcheng

AU - Nakajima, Kazuki

AU - Noda, Yoichi

AU - Shichino, Yuichi

AU - Iwasaki, Shintaro

AU - Suzuki, Tadashi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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