# Role of a NIMA-related kinase in neuronal microtubule stability and transport

> **NIH NIH F31** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $43,049

## Abstract

Project Summary
 The Tubulin Code, via glutamylation of tubulin tails, regulates ciliary structure, transport, and function in
the nematode C. elegans. We identified genetic suppressors of CCPP-1 deglutamylase deficiency, which
causes neurodegeneration in humans, impairment of microtubule-based transport in hippocampal neuron
culture, and neuronal ciliary degeneration in C. elegans. Mutation in the NIMA-related kinase NEKL-4/NEK10
suppresses ccpp-1-induced ciliary degeneration. In humans, NEK10 mutation causes bronchiectasis, a
disorder of mucociliary transport in the airway due to defective motile cilia. NEK10 is also important in some
cells for ciliogenesis and mitochondrial function, and is predicted to regulate several cilia-related processes
through phosphorylation activity. In C. elegans, NEKL-4 is expressed in all ciliated neurons but does not
localize to cilia, suggesting that NEKL-4 indirectly influences regulation of ciliary stability by CCPP-1 and
glutamylation. This project aims to understand the NEKL-4/NEK10 mechanism of action in neurons. First, we
will test the hypothesis that NEKL-4 localization is dynamic based on its activity state and microtubule stability.
We will determine if NEKL-4 kinase activity is essential for its function and investigate the role of NEKL-4 on
ciliary microtubule ultrastructure. Next, we will test the hypothesis that active NEKL-4 protein is involved in
dendritic mitochondrial transport. In mice, CCP1 mutation causes Purkinje cell degeneration and defects in
mitochondrial fusion and transport. We will therefore measure dendritic trafficking of mitochondria in ccpp-1
mutants using time-lapse imaging. We will also determine if nekl-4 suppresses ccpp-1 phenotypes through
alteration of trafficking dynamics. Finally, we will test the hypothesis that NEKL-4 coordinates microtubule-
based transport and/or ciliary transport by regulating kinesin motors in sensory neurons. Our innovative
approach utilizes the simple, transparent nervous system of C. elegans in combination with transgenic and
CRISPR-generated endogenous fluorescent reporters and super-resolution microscopy; this will allow us to
visualize neuronal transport in living intact animals. Our studies will provide insight to the fundamental cell
biology of microtubules, molecular motors, and cilia/flagella as well as human ciliopathies and
neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10464307
- **Project number:** 1F31NS122438-01A1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Kaiden Michael Power
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $43,049
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464307

## Citation

> US National Institutes of Health, RePORTER application 10464307, Role of a NIMA-related kinase in neuronal microtubule stability and transport (1F31NS122438-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464307. Licensed CC0.

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