Universität zu Köln

Dejanovic, Borislav and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2014). Neuronal Nitric Oxide Synthase-Dependent S-Nitrosylation of Gephyrin Regulates Gephyrin Clustering at GABAergic Synapses. J. Neurosci., 34 (23). S. 7763 - 7769. WASHINGTON: SOC NEUROSCIENCE. ISSN 0270-6474

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Abstract

Gephyrin, the principal scaffolding protein at inhibitory synapses, is essential for postsynaptic clustering of glycine and GABA type A receptors (GABA(A)Rs). Gephyrin cluster formation, which determines the strength of GABAergic transmission, is modulated by interaction with signaling proteins and post-translational modifications. Here, we show that gephyrin was found to be associated with neuronal nitric oxide synthase (nNOS), the major source of the ubiquitous and important signaling molecule NO in brain. Furthermore, we identified that gephyrin is S-nitrosylated in vivo. Overexpression of nNOS decreased the size of postsynaptic gephyrin clusters in primary hippocampal neurons. Conversely, inhibition of nNOS resulted in a loss of S-nitrosylation of gephyrin and the formation of larger gephyrin clusters at synaptic sites, ultimately increasing the number of cell surface expressed synaptic GABA(A)Rs. In conclusion, S-nitrosylation of gephyrin is important for homeostatic assembly and plasticity of GABAergic synapses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dejanovic, Borislav UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435972
DOI:	10.1523/JNEUROSCI.0531-14.2014
Journal or Publication Title:	J. Neurosci.
Volume:	34
Number:	23
Page Range:	S. 7763 - 7769
Date:	2014
Publisher:	SOC NEUROSCIENCE
Place of Publication:	WASHINGTON
ISSN:	0270-6474
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GABA(A) RECEPTOR SUBTYPES; INHIBITORY SYNAPSES; DIRECT BINDING; PLASTICITY; SUBUNIT; PHOSPHORYLATION; AGGREGATION; ACTIVATION; REQUIRES; RELEASE Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/43597