The ubiquitin-like protein Plic-1 enhances the membrane insertion of GABAA receptors by increasing their stability within the endoplasmic reticulum

Authors:
Saliba RS, Pangalos M, Moss SJ
In:
Source: J Biol Chem
Publication Date: (2008)
Issue: 283(27): 18538-44
Research Area:
Neurobiology
Cells used in publication:
293
Species: human
Tissue Origin: kidney
Neuron, hippo/cortical, rat
Species: rat
Tissue Origin: brain
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
G -aminobutyric acid receptors (GABAAR) are the major sites of fast inhibitory neurotransmission in the brain, and a critical determinant for the efficacy of neuronal inhibition is the number of these receptors that are expressed on the neuronal cell surface. GABAARs are hetero-pentamers that can be constructed from 7 subunit classes with multiple members; a, ss, (1-3), d, e(1-3) and p. Receptor assembly occurs within the endoplasmic reticulum (ER) and it is evident that transport competent combinations exiting this organelle can access the cell surface, while unassembled subunits are ubiquitinated and subject to proteasomal degradation. Here we have explored the role that the ubiquitin-like protein Plic-1, which directly interacts with GABAAR subunits plays in regulating their membrane trafficking. Using both recombinant and neuronal preparations it was apparent that Plic-1 increased the stability of ER resident GABAARs together, with an increase in the abundance of poly-ubiquitinated receptor subunits. Furthermore Plic-1 promoted cell surface expression levels by selectively increasing their rates of membrane insertion. Thus Plic-1 may play a significant role in regulating the strength of synaptic inhibition by increasing the stability of GABAARs within the secretory pathway and thereby promoting their insertion into the neuronal plasma membrane.