Neurons dispose of hyperactive kinesin into glial cells for clearance.
EMBO J
; 43(13): 2606-2635, 2024 Jul.
Article
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| MEDLINE
| ID: mdl-38806659
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.
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MEDLINE
Asunto principal:
Neuroglía
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Cilios
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Cinesinas
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
Límite:
Animals
Idioma:
En
Año:
2024
Tipo del documento:
Article