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:
CreatorsEmailORCIDORCID Put Code
Dejanovic, BorislavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Semtner, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebert, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lamkemeyer, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuser, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scher, Bernhard LuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, Jochen C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, GuenterUNSPECIFIEDorcid.org/0000-0002-2118-9338UNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INHIBITORY SYNAPSES; GABA(A) RECEPTORS; GAMMA-2 SUBUNIT; GLYCINE; TRAFFICKING; IDENTIFICATION; PROTEINS; BINDING; PHOSPHORYLATION; LOCALIZATIONMultiple languages
Biochemistry & Molecular Biology; BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43433

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