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)) receptors in neuronal membranes is a crucial factor for the efficacy of inhibitory 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 membranes. Functionally, Plic-1 facilitates GABA(A) receptor cell surface expression without affecting the rate of receptor internalization. Plic-1 also enhances the stability of intracellular GABA(A) 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 GABA(A) receptor cell surface number, which suggests that Plic-1 facilitates accumulation of these receptors in dendritic membranes.
Bedford
F K
FK
Medical Research Council Laboratory of Molecular Cell Biology and Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Kittler
J T
JT
Muller
E
E
Thomas
P
P
Uren
J M
JM
Merlo
D
D
Wisden
W
W
Triller
A
A
Smart
T G
TG
Moss
S J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D004355:Drug Stability; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014452:Ubiquitins / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020033:Protein Isoforms; D011963:Receptors, GABA-A; C107792:UBQLN1 protein, human; D014452:Ubiquitins