Research article summary (published 30 May 2002):

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

Full 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.

Author information

Author/s: Lévi, Sabine (S); Grady, R Mark (RM); Henry, Michael D (MD); Campbell, Kevin P (KP); Sanes, Joshua R (JR); Craig, Ann Marie (AM);

Affiliation: Washington University, Department of Anatomy and Neurobiology, St. Louis, Missouri 63110, USA.

Grants: NS33184 (Agency:NINDS NIH HHS) ; NS34448 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2002-Jun; vol 22 (issue 11) : pp 4274-85

Dates: Created 2002/05/31; Completed 2002/07/05; Revised 2007/11/14;

PMID: 12040032, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - deficiency; genetics; metabolism Animals Carrier Proteins - genetics; metabolism Cell Differentiation - physiology Cells, Cultured Cytoskeletal Proteins - metabolism Dystroglycans Dystrophin - deficiency; genetics; metabolism Glutamate Decarboxylase - metabolism Hippocampus Macromolecular Substances Membrane Glycoproteins - metabolism

Membrane Glycoproteins - metabolism Membrane Proteins - deficiency; genetics; metabolism Mice Mice, Inbred Strains Mice, Inbred mdx Mice, Knockout Muscular Dystrophy, Animal Neural Inhibition - physiology Neurons - cytology; metabolism Receptors, GABA-A - metabolism Synapses - metabolism; ultrastructure gamma-Aminobutyric Acid - metabolism

Associated Chemicals: Agrin (0) ; Carrier Proteins (0) ; Cytoskeletal Proteins (0) ; Dystrophin (0) ; Macromolecular Substances (0) ; Membrane Glycoproteins (0) ; Membrane Proteins (0) ; Receptors, GABA-A (0) ; gephyrin (0) ; Dystroglycans (146888-27-9) ; gamma-Aminobutyric Acid (56-12-2) ; Glutamate Decarboxylase (EC 4.1.1.15)

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