Analysis of ErbB4-Akt Signaling Activation Induced by Neurexin1β
PV(Parvalbumin)interneurons regulate the function of excitatory neurons and maintain neuronal network homeostasis.ErbB4,which is mainly localized at excitatory synapseson PV interneurons,promotes PV interneuron migration,differentiation,axonal growth,synaptic formation,etc.Currently,ErbB4 signaling cascade has received widespread attention,but its mechanism has not been fully elucidated.We have found that NRXN1β interacts with ErbB4 in the prefrontal cortex of rats,and that facilitating their binding induces excitatory synapse formation on PV interneurons,resulting in enhanced activity of PV-positive interneurons.In this study,the structural basis of NRXN1β-ErbB4 interaction was explored in HEK293T cells.The results showed that extracellular segment of NRXN1β can bind to ErbB4,while intracellular segment of NRXN1β can not.Primary cortical neurons were further incubated with NRXN1β51-363(extracellular peptide segment of NRXN1β).Phosphorylation levels of ErbB4 and Akt were increased in neurons treated with NRXN1β51-363 using immunoblotting and immunofluorescence assays.In conclusion,the interaction between ErbB4 and NRXN1β occurs on the outer side of neuronal membrane.NRXN1β-ErbB4 signaling can activate downstream Akt signaling cascade in neurons,which may be one of the mechanisms underlying PV interneuron activity enhanced by ErbB4.
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