Aberrant Dopamine Signaling Research Articles

Receptor tyrosine kinase transactivation: fine-tuning synaptic transmission

G-protein-coupled receptors generate signals that promote gene transcription through the ‘transactivation’ of receptor tyrosine kinases (RTKs) and activation of the mitogen-activated protein kinase (MAPK) cascade – a process that involves RTK autophosphorylation and endocytosis. Pioneering work now suggests that D4-dopamine-receptor-mediated transactivation of the platelet-derived growth factor β receptor has immediate effects on synaptic neurotransmission via Ca 2+-dependent inactivation of NMDA receptors. The demonstration of a physiological role for RTK transactivation in the CNS provides novel opportunities for understanding how aberrant dopamine signalling might contribute to cognitive and attention deficits associated with schizophrenia and attention-deficit hyperactivity disorder.