Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk
Cristina Lao-Peregrin,
Guoqing Xiang,
Jihye Kim,
Ipsit Srivastava,
Alexandra B. Fall,
Danielle M. Gerhard,
Piia Kohtala,
Daegeon Kim,
Minseok Song,
Mikel Garcia-Marcos,
Joshua Levitz,
Francis S. Lee
Affiliations
Cristina Lao-Peregrin
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA
Guoqing Xiang
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA
Jihye Kim
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA
Ipsit Srivastava
Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA
Alexandra B. Fall
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA
Danielle M. Gerhard
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA
Piia Kohtala
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA
Daegeon Kim
Department of Life Sciences, Yeongnam University, Gyeongsan, Gyeongbuk 38451, South Korea
Minseok Song
Department of Life Sciences, Yeongnam University, Gyeongsan, Gyeongbuk 38451, South Korea
Mikel Garcia-Marcos
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
Joshua Levitz
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author
Francis S. Lee
Department of Psychiatry, Weill Cornell Medicine. New York, NY 10065, USA; Corresponding author
Summary: Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and the physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK) TrkB and the G-protein-coupled receptor (GPCR) metabotropic glutamate receptor 5 (mGluR5) together mediate hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode switch that drives BDNF-dependent sustained, oscillatory Ca2+ signaling and enhanced MAP kinase activation. This crosstalk is mediated, in part, by synergy between Gβγ, released by TrkB, and Gαq-GTP, released by mGluR5, to enable physiologically relevant RTK/GPCR crosstalk.
