N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration.
N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration.
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DOI：
10.1073/pnas.1811100115
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发表时间：
2018-10-16
影响因子：
11.1
通讯作者：
Hatten ME
中科院分区：
文献类型：
--
作者：
Horn Z;Behesti H;Hatten ME
胶质细胞引导的神经元迁移是哺乳动物大脑皮质区域组织发生的关键步骤，需要迁移的神经元和胶质纤维表达粘附蛋白。神经元受体astrotactin（ASTN 1）调节神经胶质引导的迁移，但神经胶质配体一直是未知的。在这里，我们表明，神经元-胶质细胞的附着和神经元迁移依赖于神经钙粘蛋白（CDH2）的胶质细胞的表达和ASTN 1促进迁移的直接相互作用与神经元和胶质细胞的CDH2。因此，ASTN 1和CDH2在迁移连接处形成顺式和反式不对称桥复合物，这对于胶质细胞引导的神经元迁移至关重要。先前的研究表明，astrotactin（ASTN 1）提供了一个神经元受体胶质细胞引导的中枢神经系统迁移。在这里，我们报告说，ASTN 1结合N-钙粘蛋白（CDH2）和ASTN 1：CDH2的相互作用支持细胞间粘附。为了测试ASTN 1：CDH2结合在胶质细胞引导的神经元迁移中的功能，我们在小脑颗粒细胞和胶质细胞中产生了Cdh 2的条件性损失。颗粒细胞迁移减慢小脑切片培养后，神经元Cdh 2的条件性损失，更严重的迁移缺陷发生后，胶质Cdh 2的条件性损失。不结合CDH2的ASTN 1突变形式在颗粒细胞中的表达也减缓了迁移。此外，在体外嵌合体的颗粒细胞和神经胶质细胞显示受损的神经元-神经胶质细胞的附着在没有神经胶质细胞，但不是神经元，Cdh 2。因此，ASTN 1与神经元和胶质细胞CDH2的顺式和反式结合形成非对称神经元-胶质细胞桥复合物，其促进胶质细胞引导的神经元迁移。
Glial-guided neuronal migration is a key step in the histogenesis of cortical regions in the mammalian brain and requires the expression of adhesion proteins by the migrating neuron and the glial fiber. The neuronal receptor astrotactin (ASTN1) regulates glial-guided migration, but the glial ligand has long been unknown. Here we demonstrate that neuron–glia attachment and neuronal migration depend on glial expression of the neural cadherin (CDH2) and that ASTN1 promotes migration by a direct interaction with neuronal and glial CDH2. Thus, ASTN1 and CDH2 form a cis and trans asymmetric bridge complex in the migration junction that is essential for glial-guided neuronal migration. Prior studies demonstrate that astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell–cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss of Cdh2 in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronal Cdh2, and more severe migration defects occurred after a conditional loss of glial Cdh2. Expression in granule cells of a mutant form of ASTN1 that does not bind CDH2 also slowed migration. Moreover, in vitro chimeras of granule cells and glia showed impaired neuron–glia attachment in the absence of glial, but not neuronal, Cdh2. Thus, cis and trans bindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron–glial bridge complex that promotes glial-guided neuronal migration.
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影响因子：
3.4
作者：
Hara Y;Fukaya M;Hayashi K;Kawauchi T;Nakajima K;Sakagami H
通讯作者：
Sakagami H
DOI：
10.1146/annurev-cellbio-101512-122400
发表时间：
2013
影响因子：
11.3
作者：
Evsyukova I;Plestant C;Anton ES
通讯作者：
Anton ES
影响因子：
16.2
作者：
Franco SJ;Martinez-Garay I;Gil-Sanz C;Harkins-Perry SR;Müller U
通讯作者：
Müller U
DOI：
10.1083/jcb.100.2.384
发表时间：
1985-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hatten ME
通讯作者：
Hatten ME
DOI：
10.1073/pnas.0606701103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Prakasam, A. K.;Maruthamuthu, V.;Leckband, D. E.
通讯作者：
Leckband, D. E.