| RRC ID |
83993
|
| Author |
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.
|
| Title |
Neurons dispose of hyperactive kinesin into glial cells for clearance.
|
| Journal |
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.
|
| Volume |
43(13)
|
| Pages |
2606-2635
|
| Published |
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
|
| Resource |
| C.elegans |
tm324 |
