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 language | English |
|---|---|
| Pages (from-to) | 15900-15911 |
| Number of pages | 12 |
| Journal | Journal of Biological Chemistry |
| Volume | 294 |
| Issue number | 44 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
}
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 journal › Article
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=85074379494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074379494&partnerID=8YFLogxK
U2 - 10.1074/jbc.RA119.009491
DO - 10.1074/jbc.RA119.009491
M3 - Article
C2 - 31311856
AN - SCOPUS:85074379494
VL - 294
SP - 15900
EP - 15911
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 44
ER -