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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| Format: | Article |
| Status: | Published version |
| Publication date: | 2009 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/122461 |
| Online Access: | https://hdl.handle.net/2445/122461 |
| Access Level: | Open access |
| Keyword: | Adenosina Proteïnes Adenosine Proteins |
| _version_ | 1878733392083681280 |
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| author | Navarro Brugal, Gemma |
| author2 | 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 |
| author2_role | author author author author author author author author author author author author author |
| author_browse | Agnati, Luigi F. Aymerich, María Soledad Canela Campos, Enric I. (Enric Isidre), 1949- Casadó, Vicent Cortés Tejedor, Antonio Ferré, Sergi Franco Fernández, Rafael Fuxe, Kjell Lanciego, José Luis Lluís i Biset, Carme Mallol Montero, Josefa Marcellino, Daniel Navarro Brugal, Gemma Woods, Amina S. |
| author_facet | 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 |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_554644fb1eaeeebb76dfcd302c0fbb39 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/122461 |
| publishDate | 2009 |
| publishDateSort | 2009 |
| publisher | American Society for Biochemistry and Molecular Biology |
| publisherStr | American Society for Biochemistry and Molecular Biology |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors 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 Adenosina Proteïnes Adenosine Proteins 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. American Society for Biochemistry and Molecular Biology https://hdl.handle.net/2445/122461 |
| spellingShingle | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors Navarro Brugal, Gemma Adenosina Proteïnes Adenosine Proteins |
| status_str | publishedVersion |
| title | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors |
| title_full | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors |
| title_fullStr | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors |
| title_full_unstemmed | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors |
| title_short | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors |
| title_sort | Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors |
| topic | Adenosina Proteïnes Adenosine Proteins |
| topic_facet | Adenosina Proteïnes Adenosine Proteins |
| url | https://hdl.handle.net/2445/122461 |