A functional aspect of horizontal molecular networks has been investigated experimentally, namely the heteromerization between adenosine A(2A) and doparnine 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, A(2A), D-1, and D-2 receptors obtained in two clones of Chinese hamster ovary cells-one transfected with A(2A) and dopamine D, receptors and the other one with A(2A) and D-2 receptors. Cells were treated for 3 h with 10 mu M D-1 receptor agonist SKF 38393,50 mu M D-2-D-3 receptor agonist quinpirole, and 200 nM A(2A) receptor agonist CGS 21680. In A(2A)-D-1-cotransfected cells, caveolin-1 was found to colocalize with both A2A and D, receptors and treatment with SKF 38393 induced internalization of caveolin-1 and D-1 receptors, with a preferential internalization of D, receptors colocalized. with caveolin-1. In A(2A)-D-2-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 A2A 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.

Computer-assisted image analysis of Caveolin-1 involvement in the iternalization process of adenosine A2A-dopamine D2 Receptor heterodimers / Genedani, Susanna; D., Guidolin; Leo, Giuseppina; Filaferro, Monica; M., Torvinen; A. S., Woods; K., Fuxe; S., Ferre; Agnati, Luigi Francesco. - In: JOURNAL OF MOLECULAR NEUROSCIENCE. - ISSN 0895-8696. - STAMPA. - 26:(2005), pp. 177-184. [10.1385/JMN:26:2-3:177]

Computer-assisted image analysis of Caveolin-1 involvement in the iternalization process of adenosine A2A-dopamine D2 Receptor heterodimers

GENEDANI, Susanna;LEO, Giuseppina;FILAFERRO, Monica;AGNATI, Luigi Francesco
2005

Abstract

A functional aspect of horizontal molecular networks has been investigated experimentally, namely the heteromerization between adenosine A(2A) and doparnine 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, A(2A), D-1, and D-2 receptors obtained in two clones of Chinese hamster ovary cells-one transfected with A(2A) and dopamine D, receptors and the other one with A(2A) and D-2 receptors. Cells were treated for 3 h with 10 mu M D-1 receptor agonist SKF 38393,50 mu M D-2-D-3 receptor agonist quinpirole, and 200 nM A(2A) receptor agonist CGS 21680. In A(2A)-D-1-cotransfected cells, caveolin-1 was found to colocalize with both A2A and D, receptors and treatment with SKF 38393 induced internalization of caveolin-1 and D-1 receptors, with a preferential internalization of D, receptors colocalized. with caveolin-1. In A(2A)-D-2-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 A2A 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.
2005
26
177
184
Computer-assisted image analysis of Caveolin-1 involvement in the iternalization process of adenosine A2A-dopamine D2 Receptor heterodimers / Genedani, Susanna; D., Guidolin; Leo, Giuseppina; Filaferro, Monica; M., Torvinen; A. S., Woods; K., Fuxe; S., Ferre; Agnati, Luigi Francesco. - In: JOURNAL OF MOLECULAR NEUROSCIENCE. - ISSN 0895-8696. - STAMPA. - 26:(2005), pp. 177-184. [10.1385/JMN:26:2-3:177]
Genedani, Susanna; D., Guidolin; Leo, Giuseppina; Filaferro, Monica; M., Torvinen; A. S., Woods; K., Fuxe; S., Ferre; Agnati, Luigi Francesco
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/310338
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