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Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic capsaicin stimulation

Laffray, Sophie and Tan, Kelly and Dulluc, Josette and Bouali-Benazzouz, Rabia and Calver, Andrew R. and Nagy, Frédéric and Landry, Marc. (2007) Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic capsaicin stimulation. European Journal of Neuroscience, 25 (5). pp. 1402-1416.

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Official URL: http://edoc.unibas.ch/50656/

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Physiopathology of basal ganglia neuronal subcircuits (Tan)
UniBasel Contributors:Tan, Kelly
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:0953-816X
e-ISSN:1460-9568
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:28 Nov 2017 08:06
Deposited On:28 Nov 2017 08:06

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