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Structure and function of adenosine receptor heteromers

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Abstract

Adenosine is one of the most ancient signaling molecules and has receptors in both animals and plants. In mammals there are four specific receptors, A1, A2A, A2B, and A3, which belong to the superfamily of G-protein-coupled receptors (GPCRs). Evidence accumulated in the last 20 years indicates that GPCRs are often expressed as oligomeric complexes formed by a number of equal (homomers) or different (heteromers) receptors. This review presents the data showing the occurrence of heteromers formed by A1 and A2A, A2A and A2B, and A2A and A3 receptors highlighting (i) their tetrameric structural arrangements, and (ii) the functional diversity that those heteromers provide to adenosinergic signaling.

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Funding

This work was partially supported by grants SAF2017-84117, RTI2018-098830-B-I00, and PID2019-109240RB-I00 from the Spanish Ministry of Science and Innovation (MICINN) and or Science, Innovation and Universities; they may include EU FEDER funds. C.L.T. is the recipient of a FPI fellowship (BES-2017-081872). The laboratory of the University of Barcelona is considered of excellence by the Regional Catalonian Government (grup consolidat #2017 SGR 1497), which does not provide any specific funding for personnel, equipment and reagents or for payment of services.

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  1. Molecular Neurobiology Laboratory, Department Biochemistry and Molecular Biomedicine, School of Biology, University of Barcelona, Diagonal 643, Catalonia, 08028, Barcelona, Spain

    Rafael Franco & Joan Serrano-Marín

  2. Centro de Investigación en Red, Enfermedades Neurodegenerativas (CiberNed), Instituto de Salud Carlos iii, Madrid, Spain

    Rafael Franco & Gemma Navarro

  3. Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Campus Universitari, 08193, Bellaterra (Barcelona), Spain

    Arnau Cordomí, Claudia Llinas del Torrent & Leonardo Pardo

  4. Department of Biochemistry and Physiology, School of Pharmacy and Food Science, University of Barcelona, Catalonia, Barcelona, Spain

    Alejandro Lillo & Gemma Navarro

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RF and LP conceived the idea and made a design of the sections in the review. AC, AL, and GN searched and summarized the content of relevant papers in literature. JSM and CLT looked information to prepare the Figs. RF wrote the first draft that was edited by all authors who also approved the final version.

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Franco, R., Cordomí, A., Llinas del Torrent, C. et al. Structure and function of adenosine receptor heteromers. Cell. Mol. Life Sci. 78, 3957–3968 (2021). https://doi.org/10.1007/s00018-021-03761-6

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