Distinct functional domains of Dystroglycan regulate inhibitory synapse formation and maintenance in cerebellar Purkinje cells.

Autor: Jahncke JN; Neuroscience Graduate Program, Oregon Health & Science University, Portland, OR 97239, USA., Schnell E; Operative Care Division, Portland VA Health Care System.; Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA., Wright KM; Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 30. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1101/2024.08.29.610348
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare that they have no competing interests.
Databáze: MEDLINE
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