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

Mol Cell Neurosci. 2007 Sep;36(1):1-12. doi: 10.1016/j.mcn.2007.05.007. Epub 2007 Jun 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Calcium-Binding Proteins / metabolism*
  • Cell Line, Transformed
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism
  • Corpus Striatum / ultrastructure
  • DNA-Binding Proteins
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation / physiology*
  • Humans
  • Immunoprecipitation / methods
  • Microscopy, Immunoelectron / methods
  • Phenethylamines / pharmacology
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Rats
  • Receptors, Adenosine A2 / metabolism*
  • Transfection
  • Two-Hybrid System Techniques


  • Antihypertensive Agents
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Phenethylamines
  • Receptors, Adenosine A2
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Extracellular Signal-Regulated MAP Kinases
  • Ca-binding protein 2
  • Adenosine