Article abstract
Nature Neuroscience 11, 1402 - 1409 (2008)
Published online: 26 October 2008 | doi:10.1038/nn.2216
FGF acts as a co-transmitter through adenosine A2A receptor to regulate synaptic plasticity
Marc Flajolet1, Zhongfeng Wang2, Marie Futter1, Weixing Shen2, Nina Nuangchamnong1, Jacob Bendor1, Iwona Wallach1, Angus C Nairn1,3, D James Surmeier2 & Paul Greengard1
Abstract
Abnormalities of striatal function have been implicated in several major neurological and psychiatric disorders, including Parkinson's disease, schizophrenia and depression. Adenosine, via activation of A2A receptors, antagonizes dopamine signaling at D2 receptors and A2A receptor antagonists have been tested as therapeutic agents for Parkinson's disease. We found a direct physical interaction between the G protein–coupled A2A receptor (A2AR) and the receptor tyrosine kinase fibroblast growth factor receptor (FGFR). Concomitant activation of these two classes of receptors, but not individual activation of either one alone, caused a robust activation of the MAPK/ERK pathway, differentiation and neurite extension of PC12 cells, spine morphogenesis in primary neuronal cultures, and cortico-striatal plasticity that was induced by a previously unknown A2AR/FGFR-dependent mechanism. The discovery of a direct physical interaction between the A2A and FGF receptors and the robust physiological consequences of this association shed light on the mechanism underlying FGF functions as a co-transmitter and open new avenues for therapeutic interventions.
- Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
- Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
- Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06508, USA.
Correspondence to: Paul Greengard1 e-mail: greengard@rockefeller.edu
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