Trends in Neurosciences
Research FocusReceptor tyrosine kinase transactivation: fine-tuning synaptic transmission
Section snippets
Focal adhesion complexes and synaptic transmission
One mechanism by which GPCRs modulate NMDA receptor signalling is via focal adhesion complexes. Focal adhesions are points of contact between cells and the extracellular matrix that can be utilized as scaffolds for the assembly of protein complexes required for GPCR-dependent activation of the Ras–mitogen-activated-protein kinase (MAPK) signalling cascade [10]. GPCR activation in fibroblasts leads to the rapid tyrosine phosphorylation and activation of p125 focal adhesion kinase (FAK), a
RTK transactivation and GPCR signaling
GPCRs and RTKs regulate many of the same signals and molecular intermediates involved in the MAPK signalling cascade and this convergence involves the transactivation of RTKs by GPCRs 3, 7, 8, 9. It is now appreciated that the receptors for epidermal growth factor (EGF), platelet-derived growth factor (PDGF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) can be transactivated in response to GPCR activation 3, 9, 15, 16. The transactivation of RTKs by GPCRs appears to
RTK transactivation and synaptic transmission
RTK transactivation by GPCRs leading to the activation of MAPK signalling is thought to regulate cell proliferation and differentiation, rather than short-term regulatory events [3]. This is what is unique and exciting about the recent study published in the journal Neuron by Kotecha and co-workers [32]. In their study, Kotecha et al. [32] demonstrate that D4 dopamine receptor transactivation of the PDGFβ receptor depresses excitatory neurotransmission mediated by the NMDA subtype of glutamate
Acknowledgements
I am the recipient of a Heart and Stroke Foundation of Canada MacDonald Scholarship, Premier's Research Excellence Award and Canada Research Chair in Molecular Neuroscience. This work was supported by CIHR grant MA-15506.
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