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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