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Intracellular Calcium Levels Determine Differential Modulation of Allosteric Interactions within G Protein-Coupled Receptor Heteromers

Navarro, G, Aguinaga, D, Moreno, E, Hradsky, J, Reddy, PP, Cortés, A, Mallol, J, Casadó, V, Mikhaylova, M, Kreutz, MR, Lluís, C, Canela, E, McCormick, P and Ferré, S (2014) Intracellular Calcium Levels Determine Differential Modulation of Allosteric Interactions within G Protein-Coupled Receptor Heteromers Chemistry and Biology, 21 (11). pp. 1546-1556.

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Abstract

The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

Item Type: Article
Subjects : Veterinary Medicine
Authors :
NameEmailORCID
Navarro, GUNSPECIFIEDUNSPECIFIED
Aguinaga, DUNSPECIFIEDUNSPECIFIED
Moreno, EUNSPECIFIEDUNSPECIFIED
Hradsky, JUNSPECIFIEDUNSPECIFIED
Reddy, PPUNSPECIFIEDUNSPECIFIED
Cortés, AUNSPECIFIEDUNSPECIFIED
Mallol, JUNSPECIFIEDUNSPECIFIED
Casadó, VUNSPECIFIEDUNSPECIFIED
Mikhaylova, MUNSPECIFIEDUNSPECIFIED
Kreutz, MRUNSPECIFIEDUNSPECIFIED
Lluís, CUNSPECIFIEDUNSPECIFIED
Canela, EUNSPECIFIEDUNSPECIFIED
McCormick, Pp.mccormick@surrey.ac.ukUNSPECIFIED
Ferré, SUNSPECIFIEDUNSPECIFIED
Date : 20 November 2014
Identification Number : https://doi.org/10.1016/j.chembiol.2014.10.004
Copyright Disclaimer : © 2014 This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:46
Last Modified : 18 May 2017 12:43
URI: http://epubs.surrey.ac.uk/id/eprint/829147

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