Clptm1 Limits Forward Trafficking of GABAAReceptors to Scale Inhibitory Synaptic Strength

In contrast with numerous studies of glutamate receptor-associated proteins and their involvement in the modulation of excitatory synapses, much less is known about mechanisms controlling postsynaptic GABAAreceptor (GABAAR) numbers. Using tandem affinity purification from tagged GABAAR γ2 subunit tr...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2018-02, Vol.97 (3), p.596
Main Authors: Ge, Yuan, Kang, Yunhee, Cassidy, Robert M, Kyung-Mee Moon, Lewis, Renate, Rachel OL Wong, Foster, Leonard J, Craig, Ann Marie
Format: Article
Language:English
Subjects:
Cleft lip/palate
Endoplasmic reticulum
Glutamic acid receptors
Glycine
Hippocampus
Homeostatic plasticity
Mass spectrometry
Nervous system
Ontology
Proteins
Rodents
Scaling
Scientific imaging
Synaptic strength
Synaptic transmission
Transgenic animals
Transgenic mice
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
γ-Aminobutyric acid A receptors
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Summary:In contrast with numerous studies of glutamate receptor-associated proteins and their involvement in the modulation of excitatory synapses, much less is known about mechanisms controlling postsynaptic GABAAreceptor (GABAAR) numbers. Using tandem affinity purification from tagged GABAAR γ2 subunit transgenic mice and proteomic analysis, we isolated several GABAAR-associated proteins, including Cleft lip and palate transmembrane protein 1 (Clptm1). Clptm1 interacted with all GABAAR subunits tested and promoted GABAAR trapping in the endoplasmic reticulum. Overexpression of Clptm1 reduced GABAAR-mediated currents in a recombinant system, in cultured hippocampal neurons, and in brain, with no effect on glycine or AMPA receptor-mediated currents. Conversely, knockdown of Clptm1 increased phasic and tonic inhibitory transmission with no effect on excitatory synaptic transmission. Furthermore, altering the expression level of Clptm1 mimicked activity-induced inhibitory synaptic scaling. Thus, in complement to other GABAAR-associated proteins that promote receptor surface expression, Clptm1 limits GABAAR forward trafficking and regulates inhibitory homeostatic plasticity.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2017.12.038