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Molecular mechanism for generating and regenerating neuronal network by CNR family

CNR家族生成和再生神经网络的分子机制

基本信息

批准号：
14104025
负责人：
YAGI Takeshi
金额：
$ 72.88万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14104025/
关键词：
cadherin neuron neural network divesity genome gene cluster gene regulation mouse 脳神経行動 Fyn CNR 脳シナプストカドヘリン心

项目摘要

Brain is a complex system which is composed of enormous number of diverse neurons. CNR/Protocadherin (Pcdh) family is constituted with gene cluster like immunoglobulin and T cell receptor genes. The CNR/Pcdh proteins are localized in synapses and developmental axons. They are differentially expressed in individual neurons. In this project, to examine molecular mechanism for neural network formation and rearrangement, we focus to the CNR/Pcdh family in the brain. This project demonstrated that 1) mouse CNR1 (Pcdha4) protein gains cell adhesion activity via active integrin proteins, 2) we firstly revealed protein structure of protocadherin family by NMR spectroscopy, 3) CNR/Pcdha proteins highly express in the developmental axons and decline from initial formation of myelin, and their down regulation is regulated by myelination, 4) producing gene converted mice of the CNR/Pcdha family reveals their essential roles for precise neural network formation, and 5) we discover novel gene regulation of the CNR/Pcdh gene clusters in individual Purkinje cells. Thus this project successfully reveals that the diverse CNR/Pcdh family molecules play roles for cell adhesion activity, establishment for neuronal diversity and neural network formation in the brain.

大脑是一个由大量不同种类的神经元组成的复杂系统。CNR/Protocadherin(Pcdh)家族由免疫球蛋白和T细胞受体等基因簇组成。CNR/Pcdh蛋白定位于突触和发育轴突。它们在单个神经元中有不同的表达。在这个项目中，为了研究神经网络形成和重排的分子机制，我们集中在大脑中的CNR/Pcdh家族。本项目证明了1)小鼠CNR1(Pcdha4)蛋白通过激活的整合素蛋白获得细胞黏附活性；2)我们首次通过核磁共振波谱揭示了Protocadherin家族的蛋白质结构；3)CNR/Pcdha蛋白在发育轴突中高表达并从最初的髓鞘形成开始下降，它们的下调受髓鞘形成的调节；4)CNR/Pcdha家族的基因转化小鼠揭示了它们对精确的神经网络形成的关键作用；以及5)我们在单个Purkinje细胞中发现了CNR/Pcdh基因簇的新的基因调控。因此，该项目成功地揭示了不同的CNR/Pcdh家族分子在大脑中对细胞黏附活性、神经元多样性的建立和神经网络的形成起作用。