Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.

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 (GABAARs). Here, we id...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Borislav Dejanovic, Marcus Semtner, Silvia Ebert, Tobias Lamkemeyer, Franziska Neuser, Bernhard Lüscher, Jochen C Meier, Guenter Schwarz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e6cf87bccb0541ceb1903100e4195d4e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e6cf87bccb0541ceb1903100e4195d4e
record_format	dspace
spelling	oai:doaj.org-article:e6cf87bccb0541ceb1903100e4195d4e2021-11-25T05:33:02ZPalmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.1544-91731545-788510.1371/journal.pbio.1001908https://doaj.org/article/e6cf87bccb0541ceb1903100e4195d4e2014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25025157/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Postsynaptic 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 (GABAARs). Here, we identified palmitoylation of gephyrin as an important mechanism of strengthening GABAergic synaptic transmission, which is regulated by GABAAR 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.Borislav DejanovicMarcus SemtnerSilvia EbertTobias LamkemeyerFranziska NeuserBernhard LüscherJochen C MeierGuenter SchwarzPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 12, Iss 7, p e1001908 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Borislav Dejanovic Marcus Semtner Silvia Ebert Tobias Lamkemeyer Franziska Neuser Bernhard Lüscher Jochen C Meier Guenter Schwarz Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.
description	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 (GABAARs). Here, we identified palmitoylation of gephyrin as an important mechanism of strengthening GABAergic synaptic transmission, which is regulated by GABAAR 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.
format	article
author	Borislav Dejanovic Marcus Semtner Silvia Ebert Tobias Lamkemeyer Franziska Neuser Bernhard Lüscher Jochen C Meier Guenter Schwarz
author_facet	Borislav Dejanovic Marcus Semtner Silvia Ebert Tobias Lamkemeyer Franziska Neuser Bernhard Lüscher Jochen C Meier Guenter Schwarz
author_sort	Borislav Dejanovic
title	Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.
title_short	Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.
title_full	Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.
title_fullStr	Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.
title_full_unstemmed	Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.
title_sort	palmitoylation of gephyrin controls receptor clustering and plasticity of gabaergic synapses.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e6cf87bccb0541ceb1903100e4195d4e
work_keys_str_mv	AT borislavdejanovic palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT marcussemtner palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT silviaebert palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT tobiaslamkemeyer palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT franziskaneuser palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT bernhardluscher palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT jochencmeier palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses AT guenterschwarz palmitoylationofgephyrincontrolsreceptorclusteringandplasticityofgabaergicsynapses
_version_	1718414670881095680

Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses.

Ejemplares similares