Differential regulation of the postsynaptic clustering of γ-aminobutyric acid type A GABAA receptors by collybistin isoforms

T T Chiou; B Bonhomme; H Jin; C P Miralles; H Xiao; Z Fu; Robert J Harvey; K Harvey; S Vicini; A L De Blas

doi:10.1074/jbc.M111.236190

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Differential regulation of the postsynaptic clustering of γ-aminobutyric acid type A GABAA receptors by collybistin isoforms

Journal article

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Differential regulation of the postsynaptic clustering of γ-aminobutyric acid type A GABAA receptors by collybistin isoforms

T T Chiou, B Bonhomme, H Jin, C P Miralles, H Xiao, Z Fu, Robert J Harvey, K Harvey, S Vicini and A L De Blas

Journal of Biological Chemistry, Vol.286(25), pp.22456-22468

2011

DOI: https://doi.org/10.1074/jbc.M111.236190

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Abstract

GABA Receptors

neurodifferentiation

neuron

receptor regulation

synapses

ARHGEF9

collybistin

gephyrin

neuroligin 2

synapse formation

Collybistin promotes submembrane clustering of gephyrin and is essential for the postsynaptic localization of gephyrin and γ-aminobutyric acid type A (GABA A) receptors at GABAergic synapses in hippocampus and amygdala. Four collybistin isoforms are expressed in brain neurons; CB2 and CB3 differ in the C terminus and occur with and without the Src homology 3 (SH3) domain. We have found that in transfected hippocampal neurons, all collybistin isoforms (CB2 SH3+, CB2 SH3-, CB3 SH3+, and CB3 SH3-) target to and concentrate at GABAergic postsynapses. Moreover, in non-transfected neurons, collybistin concentrates at GABAergic synapses. Hippocampal neurons co-transfected with CB2 SH3- and gephyrin developed very large postsynaptic gephyrin and GABA A receptor clusters (superclusters). This effect was accompanied by a significant increase in the amplitude of miniature inhibitory postsynaptic currents. Co-transfection with CB2 SH3+ and gephyrin induced the formation of many (supernumerary) non-synaptic clusters. Transfection with gephyrin alone did not affect cluster number or size, but gephyrin potentiated the clustering effect of CB2 SH3- or CB2 SH3+. Co-transfection with CB2 SH3- or CB2 SH3+ and gephyrin did not affect the density of presynaptic GABAergic terminals contacting the transfected cells, indicating that collybistin is not synaptogenic. Nevertheless, the synaptic superclusters induced by CB2 SH3- and gephyrin were accompanied by enlarged presynaptic GABAergic terminals. The enhanced clustering of gephyrin and GABA A receptors induced by collybistin isoforms was not accompanied by enhanced clustering of neuroligin 2. Moreover, during the development of GABAergic synapses, the clustering of gephyrin and GABA A receptors preceded the clustering of neuroligin 2. We propose a model in which the SH3- isoforms play a major role in the postsynaptic accumulation of GABA A receptors and in GABAergic synaptic strength. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Details

Title: Differential regulation of the postsynaptic clustering of γ-aminobutyric acid type A GABAA receptors by collybistin isoforms
Authors: T T Chiou (Author) - University of Connecticut, United States
B Bonhomme (Author) - University of Connecticut, United States
H Jin (Author) - University of Connecticut, United States
C P Miralles (Author) - University of Connecticut, United States
H Xiao (Author) - University of Connecticut, United States
Z Fu (Author) - Georgetown University School of Medicine, United States
Robert J Harvey (Author) - University College London, United Kingdom
K Harvey (Author) - University College London, United Kingdom
S Vicini (Author) - Georgetown University School of Medicine, United States
A L De Blas (Author) - University of Connecticut, United States
Publication details: Journal of Biological Chemistry, Vol.286(25), pp.22456-22468
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
Date published: 2011
DOI: 10.1074/jbc.M111.236190
ISSN: 0021-9258; 0021-9258
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451434802621
Output Type: Journal article

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Web Of Science research areas: Biochemistry & Molecular Biology

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