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Molecular and functional heterogeneity of GABAergic synapses

Fritschy, Jean-Marc ; Panzanelli, Patrizia ; Tyagarajan, Shiva

In: Cellular and Molecular Life Sciences, 2012, vol. 69, no. 15, p. 2485-2499

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    Title
    • Molecular and functional heterogeneity of GABAergic synapses
    Author
    • Fritschy, Jean-Marc. Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland
    • Panzanelli, Patrizia. Department of Anatomy, Pharmacology and Forensic Medicine and National Institute of Neuroscience-Italy, University of Turin, Turin, Italy
    • Tyagarajan, Shiva. Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Cellular and Molecular Life Sciences, 2012, vol. 69, no. 15, p. 2485-2499. SP Birkhäuser Verlag Basel
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:313135
    Summary
    Knowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABAA receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABAA receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABAA receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses