Gephyrin, the enigmatic organizer at GABAergic synapses
- 1Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University Vienna, Vienna, Austria
- 2School of Medicine, Tufts University, Boston, MA, USA
- 3Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
GABAA receptors are clustered at synaptic sites to achieve a high density of postsynaptic receptors opposite the input axonal terminals. This allows for an efficient propagation of GABA mediated signals, which mostly result in neuronal inhibition. A key organizer for inhibitory synaptic receptors is the 93 kDa protein gephyrin that forms oligomeric superstructures beneath the synaptic area. Gephyrin has long been known to be directly associated with glycine receptor β subunits that mediate synaptic inhibition in the spinal cord. Recently, synaptic GABAA receptors have also been shown to directly interact with gephyrin and interaction sites have been identified and mapped within the intracellular loops of the GABAA receptor α1, α2, and α3 subunits. Gephyrin-binding to GABAA receptors seems to be at least one order of magnitude weaker than to glycine receptors (GlyRs) and most probably is regulated by phosphorylation. Gephyrin not only has a structural function at synaptic sites, but also plays a crucial role in synaptic dynamics and is a platform for multiple protein-protein interactions, bringing receptors, cytoskeletal proteins and downstream signaling proteins into close spatial proximity.
Keywords: GABAA receptors, gephyrin, receptor clustering, synapse formation, inhibitory synapse
Citation: Tretter V, Mukherjee J, Maric H-M, Schindelin H, Sieghart W and Moss SJ (2012) Gephyrin, the enigmatic organizer at GABAergic synapses. Front. Cell. Neurosci. 6:23. doi: 10.3389/fncel.2012.00023
Received: 04 December 2011; Accepted: 23 April 2012;
Published online: 15 May 2012.
Edited by:Enrico Cherubini, International School for Advanced Studies, Italy
Reviewed by:Antoine Triller, Ecole normale supérieure, France
Theofilos Papadopoulos, Max-Planck Institute of Experimental Medicine, Germany
Copyright: © 2012 Tretter, Mukherjee, Maric, Schindelin, Sieghart and Moss. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Verena Tretter, Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, 1090 Vienna, Austria. e-mail: firstname.lastname@example.org