The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface expression and function of the receptor.

Heptaspanning membrane also known as G protein-coupled receptors (GPCR) do interact with a variety of intracellular proteins whose function is regulate receptor traffic and/or signaling. Using a yeast two-hybrid screen, NECAB2, a neuronal calcium binding protein, was identified as a binding partner for the adenosine A(2A) receptor (A(2A)R) interacting with ...
its C-terminal domain. Co-localization, co-immunoprecipitation and pull-down experiments showed a close and specific interaction between A(2A)R and NECAB2 in both transfected HEK-293 cells and also in rat striatum. Immunoelectron microscopy detection of NECAB2 and A(2A)R in the rat striatopallidal structures indicated that both proteins are co-distributed in the same glutamatergic nerve terminals. The interaction of NECAB2 with A(2A)R modulated the cell surface expression, the ligand-dependent internalization and the receptor-mediated activation of the MAPK pathway. Overall, these results show that A(2A)R interacts with NECAB2 in striatal neurones co-expressing the two proteins and that the interaction is relevant for A(2A)R function.
Mesh Terms:
Adenosine, Animals, Antihypertensive Agents, Calcium-Binding Proteins, Cell Line, Transformed, Cell Membrane, Corpus Striatum, DNA-Binding Proteins, Dose-Response Relationship, Drug, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Humans, Immunoprecipitation, Microscopy, Immunoelectron, Phenethylamines, Protein Binding, Protein Structure, Tertiary, Rats, Receptors, Adenosine A2, Transfection, Two-Hybrid System Techniques
Mol. Cell. Neurosci.
Date: Sep. 01, 2007
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