A2A-D2 heteromers on striatal astrocytes: Biochemical and biophysical evidence

Simone Pelassa, Diego Guidolin, Arianna Venturini, Monica Averna, Giulia Frumento, Letizia Campanini, Rosa Bernardi, Pietro Cortelli, Giovanna Calandra Buonaura, Guido Maura, Luigi F. Agnati, Chiara Cervetto, Manuela Marcoli

Research output: Contribution to journalArticle

Abstract

Our previous findings indicate that A2A and D2 receptors are co-expressed on adult rat striatal astrocytes and on the astrocyte processes, and that A2A-D2 receptor–receptor interaction can control the release of glutamate from the processes. Functional evidence suggests that the receptor– receptor interaction was based on heteromerization of native A2A and D2 receptors at the plasma membrane of striatal astrocyte processes. We here provide biochemical and biophysical evidence confirming that receptor–receptor interaction between A2A and D2 receptors at the astrocyte plasma membrane is based on A2A-D2 heteromerization. To our knowledge, this is the first direct demonstration of the ability of native A2A and D2 receptors to heteromerize on glial cells. As striatal astrocytes are recognized to be involved in Parkinson’s pathophysiology, the findings that adenosine A2A and dopamine D2 receptors can form A2A-D2 heteromers on the astrocytes in the striatum (and that these heteromers can play roles in the control of the striatal glutamatergic transmission) may shed light on the molecular mechanisms involved in the pathogenesis of the disease.

Original languageEnglish
Article number2457
JournalInternational Journal of Molecular Sciences
Volume20
Issue number10
DOIs
Publication statusPublished - May 2 2019

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Keywords

  • A2A-D2 heteromers
  • Co-immunoprecipitation
  • Proximity ligation assay
  • Rat striatum
  • Striatal astrocyte processes
  • Striatal slices

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Pelassa, S., Guidolin, D., Venturini, A., Averna, M., Frumento, G., Campanini, L., Bernardi, R., Cortelli, P., Buonaura, G. C., Maura, G., Agnati, L. F., Cervetto, C., & Marcoli, M. (2019). A2A-D2 heteromers on striatal astrocytes: Biochemical and biophysical evidence. International Journal of Molecular Sciences, 20(10), [2457]. https://doi.org/10.3390/ijms20102457