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GABAA receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1

Abstract

Controlling the number of functional γ-aminobutyric acid A (GABAA) receptors in neuronal membranes is a crucial factor for the efficacy of inhibitory neurotransmission. Here we describe the direct interaction of GABAA receptors with the ubiquitin-like protein Plic-1. Furthermore, Plic-1 is enriched at inhibitory synapses and is associated with subsynaptic membranes. Functionally, Plic-1 facilitates GABAA receptor cell surface expression without affecting the rate of receptor internalization. Plic-1 also enhances the stability of intracellular GABAA receptor subunits, increasing the number of receptors available for insertion into the plasma membrane. Our study identifies a previously unknown role for Plic-1, a modulation of GABAA receptor cell surface number, which suggests that Plic-1 facilitates accumulation of these receptors in dendritic membranes.

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Figure 1: Identification of an interaction between GABAA receptors and Plic-1.
Figure 2: Interaction of Plic-1 and GABAA receptors in neurons and recombinant systems.
Figure 3: Colocalization of Plic-1 with GABAA receptors.
Figure 4: Ultrastructural localization of Plic-1 in neurons.
Figure 5: Functional regulation of GABAA receptors by the Plic-1-blocking peptide pepPBα.
Figure 6: Further characterization of the effects of pepPBα on GABAA receptor function.
Figure 7: Plic-1 modulates cell surface expression of GABAA receptors.
Figure 8: GABAA receptor subunits are stabilized by Plic-1.

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Acknowledgements

This work was supported by the MRC, the Wellcome Trust and the Institut de Recherche sur la Moelle Epinière.

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Correspondence to Stephen J. Moss.

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Bedford, F., Kittler, J., Muller, E. et al. GABAA receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1. Nat Neurosci 4, 908–916 (2001). https://doi.org/10.1038/nn0901-908

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