論文 - 詳細
| RRC ID | 84113 |
|---|---|
| 著者 | Kendler J, Wӧls F, Thapliyal S, Arcalis E, Gabriel H, Kubitschek S, Malzl D, Strobl MR, Palmberger D, Luber T, Unverzagt C, Paschinger K, Glauser DA, Wilson IBH, Yan S. |
| タイトル | N-glycan core tri-fucosylation requires Golgi α-mannosidase III activity that impacts nematode growth and behavior. |
| ジャーナル | J Biol Chem |
| Abstract |
N-glycans with complex core chitobiose modifications are observed in various free-living and parasitic nematodes but are absent in mammals. Using Caenorhabditis elegans as a model, we demonstrated that the core N-acetylglucosamine (GlcNAc) residues are modified by three fucosyltransferases (FUTs), namely FUT-1, FUT-6, and FUT-8. Interestingly, FUT-6 can only fucosylate N-glycans lacking the α1,6-mannose upper arm, indicating that a specific α-mannosidase is required to generate substrates for subsequent FUT-6 activity. By analyzing the N-glycomes of aman-3 KOs using offline HPLC-MALDI-TOF MS/MS, we observed that the absence of aman-3 abolishes α1,3-fucosylation of the distal GlcNAc of N-glycans, which suggests that AMAN-3 is the relevant mannosidase on whose action FUT-6 depends. Enzymatic characterization of recombinant AMAN-3 and confocal microscopy studies using a knock-in strain (aman-3::eGFP) demonstrated a Golgi localization. In contrast to the classical Golgi α-mannosidase II (AMAN-2), AMAN-3 displayed a cobalt-dependent α1,6-mannosidase activity toward N-glycans. Using AMAN-3 and other C. elegans glycoenzymes, we were able to mimic nematode N-glycan biosynthesis in vitro by remodeling a fluorescein conjugated-glycan and generate a tri-fucosylated structure. In addition, using a high-content computer-assisted C. elegans analysis platform, we observed that aman-3 deficient worms display significant developmental delays, morphological, and behavioral alterations in comparison to the WT. Our data demonstrated that AMAN-3 is a Golgi α-mannosidase required for core fucosylation of the distal GlcNAc of N-glycans. This enzyme is essential for the formation of the unusual tri-fucosylated chitobiose modifications in nematodes, which may play important roles in nematode development and behavior. |
| 巻・号 | 300(12) |
| ページ | 107944 |
| 公開日 | 2024-12-1 |
| DOI | 10.1016/j.jbc.2024.107944 |
| PII | S0021-9258(24)02446-3 |
| PMID | 39481603 |
| PMC | PMC11697051 |
| MeSH | Animals Caenorhabditis elegans* / enzymology Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Fucose / metabolism Fucosyltransferases / genetics Fucosyltransferases / metabolism Glycosylation Golgi Apparatus* / enzymology Golgi Apparatus* / metabolism Polysaccharides* / metabolism alpha-Mannosidase* / genetics alpha-Mannosidase* / metabolism |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 19 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2725 tm2530 tm5400 |