# Elucidating the mechanisms of ependymal ciliary signaling

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2024 · $424,338

## Abstract

ABSTRACT
Ependymal motile cilia are responsible for the coordinated movement of cerebrospinal fluid (CSF) along the
ventricle wall. The synchronized activity of ependymal cilia creates specific flow networks that are regulated by
behavioral state. Ependymal cilia motility can be controlled by specific compounds in the CSF to adjust fluid
flow, but little is known about the molecular and cellular mechanisms of this regulation. We propose the
hypothesis that G protein-coupled receptor (GPCR) signaling pathways are expressed and function within
ependymal cilia to modulate ciliary beat frequency. The focus of this proposal is to define the complement of
signaling receptors that localize to ependymal cilia and determine how GPCR activation impacts cilia beating
and activity-dependent ciliary localization of regulatory signaling proteins. As proof of principle, the GPCR
melanin-concentrating hormone (MCH) receptor 1 localizes to ependymal motile cilia and we find that the
GPCR signaling protein β-arrestin moves into ependymal cilia in response to MCH treatment. To assess which
other GPCRs and signaling proteins are localized to motile cilia in ependymal cells, we will perform proximity
labeling in normal and Bardet-Biedl syndrome protein deficient ependymal cells to identify low abundance and
transient ciliary signaling proteins. We will also employ pharmacological approaches to evaluate the role of
potential ciliary GPCRs in the regulation of ependymal cilia beating. Finally, we will assess potential ciliary
GPCR activation and signaling by defining the spatial organization of GPCRs, β-arrestin, and the signaling
chaperone Bbs4 within and proximal to the ciliary compartment prior to and after GPCR agonist addition. In
order to provide the necessary resolution to define the precise spatial organization, we will use expansion
microscopy, which is a cutting-edge imaging technique. The outcomes of this work will provide critical insight
into the sensory and signaling functions of ependymal motile cilia and lay the foundation to create new tools to
control ependymal cilia activity and discern the role of ependymal cilia in the mature brain.

## Key facts

- **NIH application ID:** 11039301
- **Project number:** 1R21NS140934-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** CANDICE C ASKWITH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $424,338
- **Award type:** 1
- **Project period:** 2024-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11039301

## Citation

> US National Institutes of Health, RePORTER application 11039301, Elucidating the mechanisms of ependymal ciliary signaling (1R21NS140934-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11039301. Licensed CC0.

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