論文 - 詳細
| RRC ID | 88040 |
|---|---|
| 著者 | Patil RR, Franklin LP, Jin MD, Hanna-Rose W. |
| タイトル | Adenylosuccinate synthetase deficiency and purine nucleotide cycle disruption impair neuromuscular function in Caenorhabditis elegans. |
| ジャーナル | Mol Genet Metab |
| Abstract |
The critical role of the purine nucleotide cycle (PNC) in human health is underscored by the fact that mutations in adenylosuccinate synthetase (ADSS) and adenylosuccinate lyase (ADSL), two of its three enzymes, are associated with severe inborn errors of purine metabolism. We use Caenorhabditis elegans to investigate the biological roles of the PNC and to characterize developmental and behavioral functions of ADSS and ADSL. Here we report that adss-1, which encodes ADSS in C. elegans, is required for fertility and locomotion. adss-1 loss-of-function mutants also have small body size, and their development is severely delayed. These phenotypes are shared with adsl-1, which encodes ADSL, suggesting that an intact PNC is required for C. elegans development. Interestingly, adss-1 and adsl-1 each have unique phenotypes not shared with the other. adss-1-specific phenotypes include excessive excitatory (or decreased inhibitory) synaptic transmission at the neuromuscular junction and impaired mechanosensation, suggesting an important function in the nervous system. We have also established a powerful model for further investigation of how ADSS activity impacts mobility, providing insight into the poorly understood molecular mechanisms driving phenotypic outcomes in ADSS1 deficiency. |
| 巻・号 | 146(3) |
| ページ | 109261 |
| 公開日 | 2025-11-1 |
| DOI | 10.1016/j.ymgme.2025.109261 |
| PII | S1096-7192(25)00253-7 |
| PMID | 41101294 |
| PMC | PMC12558026 |
| MeSH | Adenylosuccinate Lyase / genetics Adenylosuccinate Lyase / metabolism Adenylosuccinate Synthase* / deficiency Adenylosuccinate Synthase* / genetics Adenylosuccinate Synthase* / metabolism Animals Caenorhabditis elegans* / enzymology Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Humans Locomotion Mutation Neuromuscular Junction* / metabolism Phenotype Purine Nucleotides* / metabolism Purine-Pyrimidine Metabolism, Inborn Errors* / genetics Synaptic Transmission |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 1 |
| 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 | tm3328 |