title: NCS-1 associates with adenosine A(2A) receptors and modulates receptor function.
abstract: Modulation of G protein-coupled receptor (GPCR) signaling by local changes in intracellular calcium concentration is an established function of Calmodulin (CaM) which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca(2+)-sensor proteins that frequently associate with CaM targets with different functional outcome. In the present study we aimed to investigate if a target of CaM-the A(2A) adenosine receptor is able to associate with two other neuronal calcium binding proteins (nCaBPs), namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation experiments we show the existence of A(2A)-NCS-1 complexes in living cells whereas caldendrin did not associate with A(2A) receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A(2A) receptor intracellular signaling in a Ca(2+)-dependent manner. Taken together this study provides further evidence that neuronal Ca(2+)-sensor proteins play an important role in modulation of GPCR signaling.
authors.affiliation: Faculty of Biology, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Department of Biochemistry and Molecular Biology, University of Barcelona Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Navarro
authors.forename: Johannes
authors.initials: J
authors.lastname: Hradsky
authors.forename: Carmen
authors.initials: C
authors.lastname: Lluís
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCormick
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kreutz
authors.forename: Marina
authors.initials: M
authors.lastname: Mikhaylova