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Clptm1 Limits Forward Trafficking of GABAA Receptors to Scale Inhibitory Synaptic Strength.

ABSTRACT: 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 GABAA receptor (GABAAR) numbers. Using tandem affinity purification from tagged GABAAR ?2 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.

SUBMITTER: Ge Y 

PROVIDER: S-EPMC5810584 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Clptm1 Limits Forward Trafficking of GABA<sub>A</sub> Receptors to Scale Inhibitory Synaptic Strength.

Ge Yuan Y   Kang Yunhee Y   Cassidy Robert M RM   Moon Kyung-Mee KM   Lewis Renate R   Wong Rachel O L ROL   Foster Leonard J LJ   Craig Ann Marie AM  

Neuron 20180125 3

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 GABA<sub>A</sub> receptor (GABA<sub>A</sub>R) numbers. Using tandem affinity purification from tagged GABA<sub>A</sub>R γ2 subunit transgenic mice and proteomic analysis, we isolated several GABA<sub>A</sub>R-associated proteins, including Cleft lip and palate transmembrane protein 1 (Clptm1). Clpt  ...[more]

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