# Mechanisms that maintain and remodel the sensory cilium

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $254,250

## Abstract

PROJECT SUMMARY
Sensory neurons concentrate and organize molecules used to detect environmental stimuli into cilia, which are
specialized microtubule-based structures on the cell surface that function as cellular antennas. The proteins
that constitute the machinery of sensory transduction are synthesized elsewhere and must be separated from
other cellular proteins and transported to the cilium. The importance of mechanisms that mediate trafficking of
proteins to the sensory cilium is illustrated by disease-causing mutations that disrupt this process. Mutations
that compromise ciliary trafficking of the photopigment rhodopsin or the enzyme guanylyl cyclase cause retinal
dystrophies marked by photoreceptor degeneration and, ultimately, blindness. Despite the importance of
protein trafficking to the cilium, its underlying molecular mechanisms remain poorly understood. We propose to
use chemosensory BAG neurons of the nematode C. elegans as a model for discovery of mechanisms that
select and transport cargo destined for the sensory cilium. Like vertebrate photoreceptor neurons, BAG
neurons use cyclic GMP as a second messenger for sensory transduction, and the enzymes and effectors that
control cyclic GMP signals and turn them into electrical signals are highly similar to those found in
photoreceptor neurons. Trafficking of proteins to BAG cilia can be measured in situ using high-resolution
fluorescence microscopy assays, and powerful genetic tools are available to acutely or chronically manipulate
specific molecular pathways in BAG neurons and determine their function in trafficking to the cilium.
Importantly, C. elegans permits discovery of novel factors that mediate ciliary trafficking through genetic
screens and biochemical approaches. We propose to use this powerful experimental system to (1) delineate a
molecular pathway that matches cargo destined for the sensory cilium with specific motors that will carry it
through the dendrite to its destination, and (2) determine how trafficking mechanisms are regulated by
physiological or developmental cues that trigger remodeling of the BAG cilium. These studies will advance
understanding of a cellular process that is essential for sensory neuron function and viability and will integrate
cellular trafficking mechanisms with physiological and developmental programs that impact sensory cilia in
vivo.

## Key facts

- **NIH application ID:** 9889126
- **Project number:** 5R21EY030187-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Niels Ringstad
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,250
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889126

## Citation

> US National Institutes of Health, RePORTER application 9889126, Mechanisms that maintain and remodel the sensory cilium (5R21EY030187-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889126. Licensed CC0.

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