Gephyrin: a master regulator of neuronal function?

被引:292
作者
Tyagarajan, Shiva K. [1 ]
Fritschy, Jean-Marc [1 ]
机构
[1] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
GAMMA-AMINOBUTYRIC-ACID; INHIBITORY SYNAPSE DEVELOPMENT; MOLYBDENUM COFACTOR BIOSYNTHESIS; GABA(A) RECEPTOR SUBTYPES; CLUSTERING PROTEIN GEPHYRIN; RAT SPINAL-CORD; HIPPOCAMPAL GABAERGIC SYNAPSES; ACTIVITY-DEPENDENT REGULATION; EXCHANGE FACTOR COLLYBISTIN; SYNTHASE KINASE 3-BETA;
D O I
10.1038/nrn3670
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The neurotransmitters GABA and glycine mediate fast synaptic inhibition by activating ligand-gated chloride channels-namely, type A GABA (GABA(A)) and glycine receptors. Both types of receptors are anchored postsynaptically by gephyrin, which self-assembles into a scaffold and interacts with the cytoskeleton. Current research indicates that postsynaptic gephyrin clusters are dynamic assemblies that are held together and regulated by multiple protein-protein interactions. Moreover, post-translational modifications of gephyrin regulate the formation and plasticity of GABAergic synapses by altering the clustering properties of postsynaptic scaffolds and thereby the availability and function of receptors and other signalling molecules. Here, we discuss the formation and regulation of the gephyrin scaffold, its role in GABAergic and glycinergic synaptic function and the implications for the pathophysiology of brain disorders caused by abnormal inhibitory neurotransmission.
引用
收藏
页码:141 / 156
页数:16
相关论文
共 206 条
[1]   Postsynaptic scaffolds of excitatory and inhibitory synapses in hippocampal neurons: Maintenance of core components independent of actin filaments and microtubules [J].
Allison, DW ;
Chervin, AS ;
Gelfand, VI ;
Craig, AM .
JOURNAL OF NEUROSCIENCE, 2000, 20 (12) :4545-4554
[2]   Ubiquitin-dependent lysosomal targeting of GABAA receptors regulates neuronal inhibition [J].
Arancibia-Carcamo, I. Lorena ;
Yuen, Eunice Y. ;
Muir, James ;
Lumb, Michael J. ;
Michels, Guido ;
Saliba, Richard S. ;
Smart, Trevor G. ;
Yan, Zhen ;
Kittler, Josef T. ;
Moss, Stephen J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (41) :17552-17557
[3]   Activity-Dependent Tuning of Inhibitory Neurotransmission Based on GABAAR Diffusion Dynamics [J].
Bannai, Hiroko ;
Levi, Sabine ;
Schweizer, Claude ;
Inoue, Takafumi ;
Launey, Thomas ;
Racine, Victor ;
Sibarita, Jean-Baptiste ;
Mikoshiba, Katsuhiko ;
Triller, Antoine .
NEURON, 2009, 62 (05) :670-682
[4]  
Barnard EA, 1998, PHARMACOL REV, V50, P291
[5]   Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism [J].
Baudouin, Stephane J. ;
Gaudias, Julien ;
Gerharz, Stefan ;
Hatstatt, Laetitia ;
Zhou, Kuikui ;
Punnakkal, Pradeep ;
Tanaka, Kenji F. ;
Spooren, Will ;
Hen, Rene ;
De Zeeuw, Chris I. ;
Vogt, Kaspar ;
Scheiffele, Peter .
SCIENCE, 2012, 338 (6103) :128-132
[6]   Regulation of postsynaptic gephyrin cluster size by protein phosphatase 1 [J].
Bausen, Melanie ;
Weltzien, Felix ;
Betz, Heinrich ;
O'Sullivan, Gregory A. .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2010, 44 (03) :201-209
[7]   Regulation of gephyrin assembly and glycine receptor synaptic stability [J].
Bedet, Cecile ;
Bruusgaard, Jo C. ;
Vergo, Sandra ;
Groth-Pedersen, Line ;
Eimer, Stefan ;
Triller, Antoine ;
Vannier, Christian .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (40) :30046-30056
[8]   Metal insertion into the molybdenum cofactor: product-substrate channelling demonstrates the functional origin of domain fusion in gephyrin [J].
Belaidi, Abdel A. ;
Schwarz, Guenter .
BIOCHEMICAL JOURNAL, 2013, 450 :149-157
[9]   Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2 [J].
Blundell, J. ;
Tabuchi, K. ;
Bolliger, M. F. ;
Blaiss, C. A. ;
Brose, N. ;
Liu, X. ;
Sudhof, T. C. ;
Powell, C. M. .
GENES BRAIN AND BEHAVIOR, 2009, 8 (01) :114-126
[10]   INHIBITORY NEUROTRANSMISSION IN RAT SPINAL-CORD - COLOCALIZATION OF GLYCINE-RECEPTOR AND GABA(A)-RECEPTOR AT GABAERGIC SYNAPTIC CONTACTS DEMONSTRATED BY TRIPLE IMMUNOFLUORESCENCE STAINING [J].
BOHLHALTER, S ;
MOHLER, H ;
FRITSCHY, JM .
BRAIN RESEARCH, 1994, 642 (1-2) :59-69