Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors

Gemma Navarro, Marisol S. Aymerich, Daniel Marcellino, Antoni Cortés, Vicent Casadó, Josefa Mallol, Enric I. Canela, Luigi Agnati, Amina S. Woods, Kjell Fuxe, Carmen Lluís, Jose Luis Lanciego, Sergi Ferré, Rafael Franco

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)28058-28068
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number41
DOIs
StatePublished - Oct 9 2009
Externally publishedYes

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Dopamine D2 Receptors
Calmodulin
Adenosine
Bioluminescence
Energy transfer
Energy Transfer
Bioluminescence Resonance Energy Transfer Techniques
Epitopes
Basal Ganglia Diseases
Adenosine A2A Receptors
Calmodulin-Binding Proteins
Oligomerization
G-Protein-Coupled Receptors
Oligomers
Proteomics
Proteins
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Navarro, G., Aymerich, M. S., Marcellino, D., Cortés, A., Casadó, V., Mallol, J., ... Franco, R. (2009). Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors. Journal of Biological Chemistry, 284(41), 28058-28068. https://doi.org/10.1074/jbc.M109.034231

Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors. / Navarro, Gemma; Aymerich, Marisol S.; Marcellino, Daniel; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I.; Agnati, Luigi; Woods, Amina S.; Fuxe, Kjell; Lluís, Carmen; Lanciego, Jose Luis; Ferré, Sergi; Franco, Rafael.

In: Journal of Biological Chemistry, Vol. 284, No. 41, 09.10.2009, p. 28058-28068.

Research output: Contribution to journalArticle

Navarro, G, Aymerich, MS, Marcellino, D, Cortés, A, Casadó, V, Mallol, J, Canela, EI, Agnati, L, Woods, AS, Fuxe, K, Lluís, C, Lanciego, JL, Ferré, S & Franco, R 2009, 'Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors', Journal of Biological Chemistry, vol. 284, no. 41, pp. 28058-28068. https://doi.org/10.1074/jbc.M109.034231
Navarro G, Aymerich MS, Marcellino D, Cortés A, Casadó V, Mallol J et al. Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors. Journal of Biological Chemistry. 2009 Oct 9;284(41):28058-28068. https://doi.org/10.1074/jbc.M109.034231
Navarro, Gemma ; Aymerich, Marisol S. ; Marcellino, Daniel ; Cortés, Antoni ; Casadó, Vicent ; Mallol, Josefa ; Canela, Enric I. ; Agnati, Luigi ; Woods, Amina S. ; Fuxe, Kjell ; Lluís, Carmen ; Lanciego, Jose Luis ; Ferré, Sergi ; Franco, Rafael. / Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 41. pp. 28058-28068.
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