Universität zu Köln

Dejanovic, Borislav, Semtner, Marcus, Ebert, Silvia, Lamkemeyer, Tobias, Neuser, Franziska, Scher, Bernhard Lu, Meier, Jochen C. and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2014). Palmitoylation of Gephyrin Controls Receptor Clustering and Plasticity of GABAergic Synapses. PLoS. Biol., 12 (7). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1545-7885

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Abstract

Postsynaptic scaffolding proteins regulate coordinated neurotransmission by anchoring and clustering receptors and adhesion molecules. Gephyrin is the major instructive molecule at inhibitory synapses, where it clusters glycine as well as major subsets of GABA type A receptors (GABA(A)Rs). Here, we identified palmitoylation of gephyrin as an important mechanism of strengthening GABAergic synaptic transmission, which is regulated by GABA(A)R activity. We mapped palmitoylation to Cys212 and Cys284, which are critical for both association of gephyrin with the postsynaptic membrane and gephyrin clustering. We identified DHHC-12 as the principal palmitoyl acyltransferase that palmitoylates gephyrin. Furthermore, gephyrin pamitoylation potentiated GABAergic synaptic transmission, as evidenced by an increased amplitude of miniature inhibitory postsynaptic currents. Consistently, inhibiting gephyrin palmitoylation either pharmacologically or by expression of palmitoylation-deficient gephyrin reduced the gephyrin cluster size. In aggregate, our study reveals that palmitoylation of gephyrin by DHHC-12 contributes to dynamic and functional modulation of GABAergic synapses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dejanovic, Borislav UNSPECIFIED UNSPECIFIED UNSPECIFIED Semtner, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebert, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lamkemeyer, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Neuser, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Scher, Bernhard Lu UNSPECIFIED UNSPECIFIED UNSPECIFIED Meier, Jochen C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-434335
DOI:	10.1371/journal.pbio.1001908
Journal or Publication Title:	PLoS. Biol.
Volume:	12
Number:	7
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1545-7885
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 INHIBITORY SYNAPSES; GABA(A) RECEPTORS; GAMMA-2 SUBUNIT; GLYCINE; TRAFFICKING; IDENTIFICATION; PROTEINS; BINDING; PHOSPHORYLATION; LOCALIZATION Multiple languages Biochemistry & Molecular Biology; Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/43433