Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation

Sabine Lévi; R Mark Grady; Michael D Henry; Kevin P Campbell; Joshua R Sanes; Ann Marie Craig

doi:10.1523/JNEUROSCI.22-11-04274.2002

Back

Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation

Journal article

Open access

Peer reviewed

Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation

Sabine Lévi, R Mark Grady, Michael D Henry, Kevin P Campbell, Joshua R Sanes and Ann Marie Craig

The Journal of neuroscience, Vol.22(11), pp.4274-4285

06/01/2002

DOI: 10.1523/JNEUROSCI.22-11-04274.2002

PMCID: PMC6758826

PMID: 12040032

Files and links (1)

url

https://doi.org/10.1523/JNEUROSCI.22-11-04274.2002View

Published (Version of record) Open Access

Abstract

The dystrophin glycoprotein complex (DGC) is a multimolecular complex that links the extracellular matrix to the cytoskeleton. The DGC is present at the skeletal neuromuscular junction and required for its maturation and maintenance. Members of the DGC are also expressed in brain. We used cultured hippocampal neurons to analyze the distribution, regulation, and role in synaptogenesis of the major transmembrane component of the DGC, dystroglycan; one of its extracellular ligands, agrin; and one of its cytoskeletal binding partners, dystrophin. alpha-Dystroglycan, beta-dystroglycan, and dystrophin clustered at a subset of inhibitory synapses containing GABA(A)R subunits alpha1, alpha2, and gamma2, and the inhibitory receptor anchoring protein gephyrin. DGC components were not detected at excitatory glutamatergic synapses. Dystroglycan is the first identified adhesive macromolecule at mature GABA synapses. Developmentally, dystroglycan clustered at synaptic loci after synaptic vesicles, GABA(A)R, and gephyrin, the latter being closely associated with GABA(A)R at all stages of synaptogenesis analyzed. Analysis of gephyrin -/-, agrin -/-, and mdx mouse hippocampal neurons in culture indicated that synaptic clustering of dystroglycan occurs independently of gephyrin, agrin, and dystrophin. In dystroglycan-deficient neurons, cultured from a conditional mutant strain, GABAergic synapses differentiated with clusters of gephyrin and GABA(A)R apposed to synaptic terminals, but these synapses did not contain detectable dystrophin. Thus the DGC is not essential for GABAergic synaptogenesis but is likely to function in modulating inhibitory synapses or conferring specialized properties on a subset of them.

Membrane Glycoproteins - metabolism

gamma-Aminobutyric Acid - metabolism

Neurons - cytology

Agrin - metabolism

Dystroglycans

Membrane Proteins - deficiency

Neural Inhibition - physiology

Synapses - metabolism

Dystrophin - deficiency

Mice, Inbred mdx

Muscular Dystrophy, Animal

Cytoskeletal Proteins - metabolism

Agrin - deficiency

Membrane Proteins - metabolism

Neurons - metabolism

Cell Differentiation - physiology

Dystrophin - metabolism

Agrin - genetics

Membrane Proteins - genetics

Cells, Cultured

Synapses - ultrastructure

Mice, Inbred Strains

Macromolecular Substances

Mice, Knockout

Carrier Proteins - genetics

Animals

Carrier Proteins - metabolism

Dystrophin - genetics

Glutamate Decarboxylase - metabolism

Mice

Receptors, GABA-A - metabolism

Hippocampus

Details

Title: Subtitle: Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation
Creators: Sabine Lévi - Washington University, Department of Anatomy and Neurobiology, St. Louis, Missouri 63110, USA
R Mark Grady
Michael D Henry
Kevin P Campbell
Joshua R Sanes
Ann Marie Craig
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.22(11), pp.4274-4285
Publisher: United States
DOI: 10.1523/JNEUROSCI.22-11-04274.2002
PMID: 12040032
PMCID: PMC6758826
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: NS34448 / NINDS NIH HHS NS33184 / NINDS NIH HHS
Language: English
Date published: 06/01/2002
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Urology; Internal Medicine
Record Identifier: 9984068382202771

Metrics

17 Record Views

145 Times Cited - Web of Science