論文 - 詳細
| RRC ID | 86957 |
|---|---|
| 著者 | Itoh K, Kurogochi M, Kaname T, Furukawa JI, Nishihara S. |
| タイトル | Neuromuscular Defects in a Drosophila Model of the Congenital Disorder of Glycosylation SLC35A2-CDG. |
| ジャーナル | Biomolecules |
| Abstract |
SLC35A2-CDG is a congenital disorder of glycosylation caused by mutations in the SLC35A2 gene encoding a Golgi-localized UDP-galactose transporter. This transporter plays an essential role in glycan synthesis by transporting UDP-galactose from the cytoplasm into the Golgi lumen. Its dysfunction leads to impaired galactose-containing glycans and various neurological symptoms, although the underlying mechanisms remain largely unknown. We identified a novel SLC35A2-CDG patient carrying a pathogenic variant (c.617_620del, p.(Gln206ArgfsTer45)) who exhibited neurological abnormalities including bilateral ventriculomegaly. To investigate the disease mechanism, we established the first Drosophila model of SLC35A2-CDG. Knockout of Ugalt, the fly ortholog of SLC35A2, resulted in embryonic lethality, indicating its essential role. Knockdown of Ugalt reduced mucin-type O-glycans on muscles and neuromuscular junctions (NMJs), without affecting N-glycans. Ugalt knockdown larvae exhibited mislocalized NMJ boutons accompanied by a deficiency in basement membrane components on muscles. This phenotype resembles that of mutants of dC1GalT1 and dGlcAT-P, both involved in mucin-type O-glycosylation. Genetic interaction between Ugalt and dC1GalT1 was confirmed through double knockdown and double heterozygous analyses. Given that Drosophila NMJs are widely used as a model for mammalian central synapses, our findings suggest that Ugalt regulates NMJ architecture via mucin-type O-glycosylation and provide insights into the molecular basis of neurological abnormalities in SLC35A2-CDG. |
| 巻・号 | 15(9) |
| 公開日 | 2025-8-29 |
| DOI | 10.3390/biom15091256 |
| PII | biom15091256 |
| PMID | 41008563 |
| PMC | PMC12467441 |
| MeSH | Animals Congenital Disorders of Glycosylation* / genetics Congenital Disorders of Glycosylation* / metabolism Congenital Disorders of Glycosylation* / pathology Disease Models, Animal Drosophila Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Glycosylation Humans Monosaccharide Transport Proteins* / genetics Monosaccharide Transport Proteins* / metabolism Mutation Neuromuscular Junction* / metabolism Neuromuscular Junction* / pathology UDP-Galactose Translocators |
| IF | 4.082 |
| 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.5 |
| リソース情報 | |
| ショウジョウバエ | 2675R-1 |