Computer-assisted image analysis of caveolin-1 involvement in the internalization process of adenosine A2A-dopamine D2 receptor heterodimers

Susanna Genedani, Diego Guidolin, Giuseppina Leo, Monica Filaferro, Maria Torvinen, Amina S. Woods, Kjell Fuxe, Sergi Ferré, Luigi F. Agnati

Research output: Contribution to journalArticle

Abstract

This paper is dedicated to Luciano Martini, Professor of Endocrinology in Milano and to Faustino Savoldi, Professor of Neurolgy in Pavia. A functional aspect of horizontal molecular networks has been investigated experimentally, namely the heteromerization between adenosine A2A and dopamine D 2 receptors and the possible role of caveolin-1 in the cotrafficking of these molecular complexes. This study has been carried out by means of computer-assisted image analysis procedure of laser images of membrane immunoreactivity of caveolin-1, A2A, D1, and D2 receptors obtained in two clones of Chinese hamster ovary cells - one transfected with A2A and dopamine D1 receptors and the other one with A2A and D2 receptors. Cells were treated for 3 h with 10 μM D1 receptor agonist SKF 38393,50 μM D 2-D3 receptor agonist quinpirole, and 200 nM A 2A receptor agonist CGS 21680. In A2A-D 1-cotransfected cells, caveolin-1 was found to colocalize with both A2A and D1 receptors and treatment with SKF 38393 induced internalization of caveolin-1 and D1 receptors, with a preferential internalization of D1 receptors colocalized with caveolin-1. In A2A-D2-cotransfected cells, caveolin-1 was found to colocalize with both A2A and D2 receptors and either CGS 21680 or quinpirole treatment induced internalization of caveolin-1 and A 2A and D2 receptors, with a preferential internalization of A2A and D2 receptors colocalized with caveolin-1. The results suggest that A2A and D2 receptors and caveolin-1 likely interact forming a macrocomplex that internalizes upon agonist treatment. These observations are discussed in the frame of receptor oligomerization and of the possible functional role of caveolin-1 in the process of co-internalization and, hence, in controlling the permanence of receptors at the plasma membrane level (prerequisite for receptor mosaic organization and plastic adjustments) and in the control of receptor desensitization.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalJournal of Molecular Neuroscience
Volume26
Issue number2-3
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Adenosine A receptor
  • Caveolin-1
  • Dopamine D receptor
  • Heteromers
  • Internalization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

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    Genedani, S., Guidolin, D., Leo, G., Filaferro, M., Torvinen, M., Woods, A. S., Fuxe, K., Ferré, S., & Agnati, L. F. (2005). Computer-assisted image analysis of caveolin-1 involvement in the internalization process of adenosine A2A-dopamine D2 receptor heterodimers. Journal of Molecular Neuroscience, 26(2-3), 177-184. https://doi.org/10.1385/JMN:26:2-3:177