NEKL-4 Regulates Microtubule Stability and Mitochondrial Health in Ciliated Neurons

Overview

Journal bioRxiv

Date 2024 Feb 26

PMID 38405845

Authors

Kaiden M Power

Ken C Nguyen

Andriele Silva

Shaneen Singh

David H Hall

Christopher Rongo

Maureen M Barr

Affiliations

Soon will be listed here.

Abstract

Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant in cilia, and its dysregulation may contribute to ciliopathies and neurodegeneration. Mutation of the deglutamylase CCP1 causes infantile-onset neurodegeneration. In loss causes age-related ciliary degradation that is suppressed by mutation in the conserved NEK10 homolog . NEKL-4 is absent from cilia, yet negatively regulates ciliary stability via an unknown, glutamylation-independent mechanism. We show that NEKL-4 was mitochondria-associated. mutants had longer mitochondria, a higher baseline mitochondrial oxidation state, and suppressed mutant lifespan extension in response to oxidative stress. A kinase-dead mutant ectopically localized to cilia and rescued degenerating microtubule doublet B-tubules. A nondegradable mutant resembled the mutant with dye filling defects and B-tubule breaks. The Dyf phenotype was suppressed by mutation in the depolymerizing kinesin-8 KLP-13/KIF19A. We conclude that NEKL-4 influences ciliary stability by activating ciliary kinesins and promoting mitochondrial homeostasis.

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