論文 - 詳細
| RRC ID | 83993 |
|---|---|
| 著者 | Xie C, Chen G, Li M, Huang P, Chen Z, Lei K, Li D, Wang Y, Cleetus A, Mohamed MA, Sonar P, Feng W, Ökten Z, Ou G. |
| タイトル | Neurons dispose of hyperactive kinesin into glial cells for clearance. |
| ジャーナル | EMBO J |
| Abstract |
Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins. |
| 巻・号 | 43(13) |
| ページ | 2606-2635 |
| 公開日 | 2024-7-1 |
| DOI | 10.1038/s44318-024-00118-0 |
| PII | 10.1038/s44318-024-00118-0 |
| PMID | 38806659 |
| PMC | PMC11217292 |
| MeSH | Amyotrophic Lateral Sclerosis / genetics Amyotrophic Lateral Sclerosis / metabolism Amyotrophic Lateral Sclerosis / pathology Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cilia* / metabolism Kinesins* / genetics Kinesins* / metabolism Mutation Neuroglia* / metabolism Neurons / metabolism |
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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 | 2 |
| 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 | tm324 |