論文 - 詳細
| RRC ID | 12703 |
|---|---|
| 著者 | Stigliano ID, Alculumbre SG, Labriola CA, Parodi AJ, D'Alessio C. |
| タイトル | Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo. |
| ジャーナル | Mol Biol Cell |
| Abstract |
Glucosidase II (GII) sequentially removes the two innermost glucose residues from the glycan (Glc(3)Man(9)GlcNAc(2)) transferred to proteins. GII also participates in cycles involving the lectin/chaperones calnexin (CNX) and calreticulin (CRT) as it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). GII is a heterodimer in which the α subunit (GIIα) bears the active site, and the β subunit (GIIβ) modulates GIIα activity through its C-terminal mannose 6-phosphate receptor homologous (MRH) domain. Here we report that, as already described in cell-free assays, in live Schizosaccharomyces pombe cells a decrease in the number of mannoses in the glycan results in decreased GII activity. Contrary to previously reported cell-free experiments, however, no such effect was observed in vivo for UGGT. We propose that endoplasmic reticulum α-mannosidase-mediated N-glycan demannosylation of misfolded/slow-folding glycoproteins may favor their interaction with the lectin/chaperone CNX present in S. pombe by prolonging the half-lives of the monoglucosylated glycans (S. pombe lacks CRT). Moreover, we show that even N-glycans bearing five mannoses may interact in vivo with the GIIβ MRH domain and that the N-terminal GIIβ G2B domain is involved in the GIIα-GIIβ interaction. Finally, we report that protists that transfer glycans with low mannose content to proteins have nevertheless conserved the possibility of displaying relatively long-lived monoglucosylated glycans by expressing GIIβ MRH domains with a higher specificity for glycans with high mannose content. |
| 巻・号 | 22(11) |
| ページ | 1810-23 |
| 公開日 | 2011-6-1 |
| DOI | 10.1091/mbc.E11-01-0019 |
| PII | mbc.E11-01-0019 |
| PMID | 21471007 |
| PMC | PMC3103398 |
| MeSH | Carbohydrate Sequence Endoplasmic Reticulum / metabolism Gene Knockout Techniques Glucosyltransferases / genetics Glucosyltransferases / metabolism Glycoproteins / metabolism* Half-Life Hexosyltransferases / metabolism Mannose / metabolism* Molecular Sequence Data Polysaccharides / chemistry Polysaccharides / metabolism Protein Folding Protein Interaction Domains and Motifs Protein Stability Protein Structure, Tertiary Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics alpha-Glucosidases / genetics alpha-Glucosidases / metabolism* alpha-Mannosidase |
| IF | 3.791 |
| 引用数 | 30 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 遺伝子材料 | pREP1-ccdB2 (RDB06519) S. pombe entry SpEnt26D11 (SPW010483). |