Neurons Dispose of Hyperactive Kinesin into Glial Cells for Clearance

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2024 May 28

PMID 38806659

Authors

Chao Xie

Guanghan Chen

Ming Li

Peng Huang

Zhe Chen

Kexin Lei

Dong Li

Yuhe Wang

Augustine Cleetus

Mohamed Aa Mohamed

Punam Sonar

Wei Feng

Zeynep Okten

Guangshuo Ou

Affiliations

Soon will be listed here.

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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