Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.

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 Ca ²⁺ signaling and enhanced MAP kinase activation. This crosstalk is mediated, in part, by synergy between Gβγ, released by TrkB, and Gα _q -GTP, released by mGluR5, to enable physiologically relevant RTK/GPCR crosstalk.
Competing Interests: Declaration of interests The authors declare that they have no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)