The clustering of GABA(A) receptor subtypes at inhibitory synapses is facilitated via the direct binding of receptor alpha 2 subunits to gephyrin.

作者: V. Tretter , T. C. Jacob , J. Mukherjee , J.-M. Fritschy , M. N. Pangalos

DOI: 10.1523/JNEUROSCI.5050-07.2008

关键词:

摘要: Classical benzodiazepine sensitive GABA(A) receptor subtypes, the major mediators of fast synaptic inhibition in brain are heteropentamers that can be assembled from alpha1-3/5, beta1-3, and gamma2 subunits, but how neurons orchestrate their selective accumulation at synapses remains obscure. We have identified a 10 amino acid hydrophobic motif within intracellular domain alpha2 subunit regulates receptors inhibitory sites on both axon initial segments dendrites mechanism dependent scaffold protein gephyrin. This was sufficient to target CD4 (cluster differentiation molecule 4) molecules synapses, also critical regulating direct binding subunits gephyrin vitro. Our results thus reveal specific subtypes containing is ability bind

参考文章(36)
U RUDOLPH, H MOHLER, GABA-based therapeutic approaches: GABAA receptor subtype functions Current Opinion in Pharmacology. ,vol. 6, pp. 18- 23 ,(2006) , 10.1016/J.COPH.2005.10.003
Christopher N. Connolly, Belinda J. Krishek, Bernard J. McDonald, Trevor G. Smart, Stephen J. Moss, Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors. Journal of Biological Chemistry. ,vol. 271, pp. 89- 96 ,(1996) , 10.1074/JBC.271.1.89
Bernhard Lüscher, Cheryl A Keller, Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses. Pharmacology & Therapeutics. ,vol. 102, pp. 195- 221 ,(2004) , 10.1016/J.PHARMTHERA.2004.04.003
Josef T Kittler, Kristina McAinsh, Stephen J Moss, Mechanisms of GABAA Receptor Assembly and Trafficking: Implications for the Modulation of Inhibitory Neurotransmission Molecular Neurobiology. ,vol. 26, pp. 251- 268 ,(2002) , 10.1385/MN:26:2-3:251
J. T. Kittler, P. Thomas, V. Tretter, Y. D. Bogdanov, V. Haucke, T. G. Smart, S. J. Moss, Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating γ-aminobutyric acid type A receptor membrane trafficking Proceedings of the National Academy of Sciences of the United States of America. ,vol. 101, pp. 12736- 12741 ,(2004) , 10.1073/PNAS.0401860101
Melissa J Alldred, Jonas Mulder-Rosi, Sue E Lingenfelter, Gong Chen, Bernhard Lüscher, Distinct γ2 Subunit Domains Mediate Clustering and Synaptic Function of Postsynaptic GABAA Receptors and Gephyrin The Journal of Neuroscience. ,vol. 25, pp. 594- 603 ,(2005) , 10.1523/JNEUROSCI.4011-04.2005
Yury Bogdanov, Guido Michels, Cecilia Armstrong-Gold, Philip G Haydon, Jon Lindstrom, Menelas Pangalos, Stephen J Moss, Synaptic GABAA receptors are directly recruited from their extrasynaptic counterparts. The EMBO Journal. ,vol. 25, pp. 4381- 4389 ,(2006) , 10.1038/SJ.EMBOJ.7601309
M. Sassoè-Pognetto, J. Kirsch, U. Grünert, U. Greferath, J. M. Fritschy, H. Möhler, H. Betz, H. Wässle, Colocalization of gephyrin and GABAA‐receptor subunits in the rat retina The Journal of Comparative Neurology. ,vol. 357, pp. 1- 14 ,(1995) , 10.1002/CNE.903570102
Peer Wulff, Thomas Goetz, Elli Leppä, Anni-Maija Linden, Massimiliano Renzi, Jerome D Swinny, Olga Y Vekovischeva, Werner Sieghart, Peter Somogyi, Esa R Korpi, Mark Farrant, William Wisden, From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nature Neuroscience. ,vol. 10, pp. 923- 929 ,(2007) , 10.1038/NN1927
Gero Miesenböck, Dino A. De Angelis, James E. Rothman, Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins Nature. ,vol. 394, pp. 192- 195 ,(1998) , 10.1038/28190