# Defining the role of C. elegans Parkin/PDR-1 in glial engulfment of neuron fragments

> **NIH NIH F31** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $40,382

## Abstract

PROJECT SUMMARY
Glia engulf fragments of live neurons in order to regulate specialized neuron endings. Amounting evidence
indicates the engulfment of neuron fragments by glia is a broad regulatory and developmental function of glia in
both the central and peripheral nervous systems. How this process is regulated under normal conditions is
unclear in any system, but it was recently shown that mis-regulation of this process contributes to early synapse
loss in mouse models of Alzheimer’s disease. Furthermore, mis-regulation of phagocytosis by Retinal Pigment
Epithelium cell in the eye may cause some forms of macular degeneration. Synapse loss and sensory
disfunction are early hallmarks of Parkinson’s disease, however the involvement of glia is unknown. Loss of
function of the E3 ubiquitin ligase Parkin contributes to the onset and progression of Parkinson’s disease. The
role of Parkin mediating mitophagy in neurons is well characterized in mammals and invertebrate models, but
despite being expressed in several glial subtypes, the functions of Parkin in glia are unknown. We have recently
shown in C. elegans that fragments of a specialized sensory neuron are engulfed by an associated glial cell.
Preliminarily, I have found that loss of function of the Parkin ortholog pdr-1 elicits a substantial increase in the
number neuron fragments engulfed by glia, demonstrating that PDR-1 inhibits engulfment by glia. C. elegans
has historically been a powerful model used to unearth the mechanisms of phagocytosis by which cells
recognize, engulf, and degrade cellular debris. I propose to use this system to probe the mechanism by which
Parkin/PDR-1 regulates glial phagocytosis of neuron fragments. I will determine the cell-specific requirements of
PDR-1, probe substrates of its E3 ligase activity that may have roles in glial engulfment, and finally ask if its role
in mitophagy has a function in glial engulfment.

## Key facts

- **NIH application ID:** 10158183
- **Project number:** 1F31NS118958-01A1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** STEPHAN RAIDERS
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,382
- **Award type:** 1
- **Project period:** 2021-03-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158183

## Citation

> US National Institutes of Health, RePORTER application 10158183, Defining the role of C. elegans Parkin/PDR-1 in glial engulfment of neuron fragments (1F31NS118958-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10158183. Licensed CC0.

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