FGF acts as a co-transmitter through adenosine A2A receptor to regulate synaptic plasticity

Marc Flajolet, Zhongfeng Wang, Marie Futter, Weixing Shen, Nina Nuangchamnong, Jacob Bendor, Iwona Wallach, Angus C. Nairn, D. James Surmeier, Paul Greengard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

142 Scopus citations


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 A 2AR/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.

Original languageEnglish (US)
Pages (from-to)1402-1409
Number of pages8
JournalNature neuroscience
Issue number12
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Neuroscience(all)


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