# Dystroglycan regulates cerebellar synapse function

> **NIH NIH F31** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary
 Dystroglycan is a scaffolding molecule composed of a transmembrane beta subunit and a non-covalently
bonded extracellular alpha subunit. The alpha subunit undergoes heavy glycosylation and it is through these
glycan chains that Dystroglycan forms protein-carbohydrate interactions with extracellular binding partners. A
failure to properly glycosylate Dystroglycan results in a form of muscular dystrophy termed dystroglycanopathy.
The muscular defects seen in dystroglycanopathies are often accompanied by neurological defects. While the
role of Dystroglycan in muscle integrity has been well described, its role in the neurological aspects of the disease
remains understudied. It is known that Dystroglycan in neuroepithelial cells is necessary for the proper migration
of neurons during development, but Dystroglycan remains at high levels throughout life, suggesting a role beyond
development. It has been shown that neuronal Dystroglycan co-localizes with certain markers of inhibitory
synapses and can interact with neurexins, a well described class of presynaptic scaffolding molecules in the
brain. Together, this suggests a potential role for Dystroglycan in the development of a subset of inhibitory
synapses, acting as a postsynaptic scaffolding molecule.
 Recent work has shown that Dystroglycan in pyramidal neurons of the hippocampus is required for the
function of a subset of inhibitory basket synapses, but other brain regions remain unexplored. This study will
focus on inhibitory synapses in the cerebellum, where Dystroglycan is present at particularly high levels in
Purkinje neurons. The proposed experiments will utilize mouse genetics, imaging, and slice physiology to dissect
the mechanism by which Dystroglycan promotes synapse formation and/or maintenance of inhibitory synapses
in cerebellar cortex. Aim 1 will identify the subset of synapses at which Dystroglycan is present and will describe
the importance of Dystroglycan in the function of these synapses. Aim 2 will then seek to dissect the role of
Dystroglycan in synapse formation and maintenance and will test the feasibility of gene therapy to rescue the
observed synaptic phenotype. Aim 3 will investigate the roles of the various domains of Dystroglycan in synapse
function: intracellular signaling from the C-tail of the beta subunit and the interaction with extracellular binding
partners via glycosylation of the alpha subunit. This work will be among the first to explore the in vivo functional
role of Dystroglycan at synapses in the brain. Furthermore, these experiments will provide understanding with
regards to how defects in Dystroglycan results in cognitive deficits in human patients suffering from
dystroglycanopathies and will aid in the development of gene therapies to treat such cognitive defects.

## Key facts

- **NIH application ID:** 10153440
- **Project number:** 1F31NS120649-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jennifer Jahncke
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-09-28 → 2023-09-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153440

## Citation

> US National Institutes of Health, RePORTER application 10153440, Dystroglycan regulates cerebellar synapse function (1F31NS120649-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10153440. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*