
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.29.610348
preprint
1
Article
Distinct functional domains of Dystroglycan regulate inhibitory synapse formation and maintenance in cerebellar Purkinje cells
Jahncke Jennifer N. http://orcid.org/0000-0003-2319-6109

Schnell Eric http://orcid.org/0000-0002-5623-5015

Wright Kevin M. http://orcid.org/0000-0001-5094-5270

30 8 2024
2024.08.29.610348https://creativecommons.org/publicdomain/zero/1.0/ To the extent possible under law, the person who associated CC0 with this work has waived all copyright and related or neighboring rights to this work.
http://biorxiv.org/lookup/doi/10.1101/2024.08.29.610348
nihpp-2024.08.29.610348.pdf
Abstract

Dystroglycan is a cell adhesion molecule that localizes to synapses throughout the nervous system. While Dystroglycan is required to maintain inhibitory synapses from cerebellar molecular layer interneurons (MLIs) onto Purkinje cells (PCs) whether initial synaptogenesis during development is dependent on Dystroglycan has not been examined. We show that conditional deletion of Dystroglycan from Purkinje cells prior to synaptogenesis results in impaired MLI:PC synapse formation and function due to reduced presynaptic inputs and abnormal postsynaptic GABA A receptor clustering. Using genetic manipulations that disrupt glycosylation of Dystroglycan or truncate its cytoplasmic domain, we show that Dystroglycan’s role in synapse function requires both extracellular and intracellular interactions, whereas synapse formation requires only extracellular interactions. Together, these findings provide molecular insight into the mechanism of inhibitory synapse formation and maintenance in cerebellar cortex.
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pmc
