Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic capsaicin stimulation
European Journal of Neuroscience. 2007-04-05; 25(5): 1402-1416
DOI: 10.1111/j.1460-9568.2007.05398.x
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1. Eur J Neurosci. 2007 Mar;25(5):1402-16.
Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic
capsaicin stimulation.
Laffray S(1), Tan K, Dulluc J, Bouali-Benazzouz R, Calver AR, Nagy F, Landry M.
Author information:
(1)INSERM U 862, Institut François Magendie, Université Bordeaux 2, Bordeaux,
France.
Gamma-aminobutyric acid type B receptors (GABAB) are G-protein-coupled receptors
that mediate GABAergic inhibition in the brain. Their functional expression is
dependent upon the formation of heterodimers between GABAB1 and GABAB2 subunits,
a process that occurs within the endoplasmic reticulum. However, the mechanisms
that regulate GABAB receptor oligomerization at the plasma membrane remain
largely unknown. We first characterized the functional cytoarchitecture of an
organotypic co-culture model of rat dorsal root ganglia and spinal cord.
Subsequently, we studied the interactions between GABAB subunits after chronic
stimulation of sensory fibres with capsaicin. Surface labelling of recombinant
proteins showed a decrease in subunit co-localization and GABAB2 labelling, after
capsaicin treatment. In these conditions, fluorescence lifetime imaging
measurements further demonstrated a loss of interactions between green
fluorescent protein-GABAB1b and t-dimer discosoma sp red fluorescent
protein-GABAB2 subunits. Finally, we established that the GABAB receptor
undergoes clathrin-dependent internalization and rapid recycling to the plasma
membrane following activation with baclofen, a GABAB agonist. However, in
cultures chronically stimulated with capsaicin, the agonist-induced endocytosis
was decreased, reflecting changes in the dimeric state of the receptor. Taken
together, our results indicate that the chronic stimulation of sensory fibres can
dissociate the GABAB heterodimer and alters its responsiveness to the endogenous
ligand. Chronic stimulation thus modulates receptor oligomerization, providing
additional levels of control of signalling.
DOI: 10.1111/j.1460-9568.2007.05398.x
PMID: 17425567 [Indexed for MEDLINE]