GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1

Controlling the number of functional gamma -aminobutyric acid A (GABA(A)) r eceptors in neuronal membranes is a crucial factor for the efficacy of inhi bitory neurotransmission. Here we describe the direct interaction of GABA(A ) receptors with the ubiquitin-like protein Plic-1. Furthermore, Plic-1 is enriched at inhibitory synapses and is associated with subsynaptic membrane s. Functionally, Plic-1 facilitates GABA(A) receptor cell surface expressio n without affecting the rate of receptor internalization. Plic-1 also enhan ces the stability of intracellular GABA(A) receptor subunits, increasing th e number of receptors available for insertion into the plasma membrane. Our study identifies a previously unknown role for Plic-1, a modulation of GAB A(A) receptor cell surface number, which suggests that Plic-1 facilitates a ccumulation of these receptors in dendritic membranes.