Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors

The Ca2+-binding protein calmodulin (CaM) has been shown to bind directly to cytoplasmic domains of some G protein-coupled receptors, including the dopamine D2 receptor. CaM binds to the N-terminal portion of the long third intracellular loop of the D2 receptor, within an Arg-rich epitope that is al...

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Detalles Bibliográficos
Autores: Navarro Brugal, Gemma, Aymerich, María Soledad, Marcellino, Daniel, Cortés Tejedor, Antonio, Casadó, Vicent, Mallol Montero, Josefa, Canela Campos, Enric I. (Enric Isidre), 1949-, Agnati, Luigi F., Woods, Amina S., Fuxe, Kjell, Lluís i Biset, Carme, Lanciego, José Luis, Ferré, Sergi, Franco Fernández, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/122461
Acceso en línea:https://hdl.handle.net/2445/122461
Access Level:acceso abierto
Palabra clave:Adenosina
Proteïnes
Adenosine
Proteins
Descripción
Sumario:The Ca2+-binding protein calmodulin (CaM) has been shown to bind directly to cytoplasmic domains of some G protein-coupled receptors, including the dopamine D2 receptor. CaM binds to the N-terminal portion of the long third intracellular loop of the D2 receptor, within an Arg-rich epitope that is also involved in the binding to Gi/o proteins and to the adenosine A2A receptor, with the formation of A2A-D2 receptor heteromers. In the present work, by using proteomics and bioluminescence resonance energy transfer (BRET) techniques, we provide evidence for the binding of CaM to the A2A receptor. By using BRET and sequential resonance energy transfer techniques, evidence was obtained for CaM-A2A-D2 receptor oligomerization. BRET competition experiments indicated that, in the A2A-D2 receptor heteromer, CaM binds preferentially to a proximal C terminus epitope of the A2A receptor. Furthermore, Ca2+ was found to induce conformational changes in the CaM-A2A-D2 receptor oligomer and to selectively modulate A2A and D2 receptor-mediated MAPK signaling in the A2A-D2 receptor heteromer. These results may have implications for basal ganglia disorders, since A2A-D2 receptor heteromers are being considered as a target for anti-parkinsonian agents.

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