Growth factor-mediated Fyn signaling regulates α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression in rodent neocortical neurons

摘要: Src-family protein tyrosine kinases (PTKs) transduce signals to regulate neuronal development and synaptic plasticity. However, the nature of their activators molecular mechanisms underlying these neural processes are unknown. Here, we show that brain-derived neurotrophic factor (BDNF) platelet-derived growth enhance expression α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor 1 2/3 proteins in rodent neocortical neurons via PTK(s). The increase AMPA levels was blocked cultured by addition a Src-family-selective PTK inhibitor. Accordingly, cultures from Fyn-knockout mice failed respond BDNF whereas those wild-type responded. Moreover, neocortex young Fyn mutants exhibited significant vivo reduction but not mRNA levels. In vitro kinase assay revealed can indeed activate kinase: It enhanced phosphorylation as well enolase supplemented exogenously. All results suggest Fyn, activated factors, plays crucial role modulating during brain development.