Neurexin1β诱导ErbB4-Akt信号通路活化研究  

Analysis of ErbB4-Akt Signaling Activation Induced by Neurexin1β

作　　者：徐岩 吴桂梅 XU Yan;WU Guimei(Jiangsu Key Laboratory of Brain Disease Bioinformation,Xuzhou Medical University,Xuzhou Jiangsu 221004)

机构地区：[1]徐州医科大学,江苏省脑病生物信息重点实验室,江苏徐州221004

出　　处：《中国科技纵横》2024年第6期158-161,共4页China Science & Technology Overview

基　　金：徐州市科技计划项目(No.KC20132)资助。

摘　　要：PV(Parvalbumin)中间神经元可调控兴奋性神经元的正常功能,并维持神经网络的平衡。ErbB4主要分布在PV中间神经元的突触部位,促进PV中间神经元的迁移、分化、轴突生长、突触形成等。目前,ErbB4信号通路在中枢神经系统中的作用受到广泛关注,但其作用机制尚未完全阐明。前期研究已证实,大鼠的前额皮层中NRXN1β与ErbB4存在相互作用,促进二者的相互作用可诱导PV中间神经元上兴奋性突触的形成,使PV阳性中间神经元活性增强。基于此,通过表达ErbB4和NRXN1β不同结构域的质粒,探讨NRXN1β与ErbB4结合的结构基础。研究发现,NRXN1β的胞外段能与ErbB4结合,而NRXN1β的胞内段并不能与ErbB4结合。进一步使用NRXN1β51-363(NRXN1β的胞外肽段)孵育原代皮层神经元,免疫印迹和免疫荧光结果发现,NRXN1β51-363使神经元中ErbB4及Akt的磷酸化水平升高。以上结果表明,NRXN1β与ErbB4的相互作用发生在细胞外侧。神经元中NRXN1β-ErbB4信号通路的激活可以使下游Akt信号活化,这一作用可能是ErbB4使PV中间神经元活性增强的机制之一。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 NRXN1βinteracts 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 NRXN1βcan bind to ErbB4,while intracellular segment of NRXN1βcan 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 NRXN1βoccurs 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.

关 键 词：PV中间神经元 神经网络 ERBB4 Neurexin1β 信号通路 

分 类 号：Q423[生物学—神经生物学]