FGF acts as a co-transmitter through adenosine A sub(2A) receptor to regulate synaptic plasticity

• Published in: Nature neuroscience Vol. 11; no. 12; pp. 1402 - 1409
• Main Authors: Flajolet, Marc, Wang, Zhongfeng, Futter, Marie, Shen, Weixing, Nuangchamnong, Nina, Bendor, Jacob, Wallach, Iwona, Nairn, Angus C, Surmeier, D James, Greengard, Paul
• Format: Journal Article
• Language: English
• Published: 01-12-2008
• ISSN: 1097-6256
• DOI: 10.1038/nn.2216

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 A sub(2A) receptors, antagonizes dopamine signaling at D2 receptors and A sub(2A) receptor antagonists have been tested as therapeutic agents for Parkinson's disease. We found a direct physical interaction between the G protein-coupled A sub(2A) receptor (A sub(2A)R) 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 sub(2A)R/FGFR-dependent mechanism. The discovery of a direct physical interaction between the A sub(2A) 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.