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N-钙黏蛋白为星形胶质细胞导向蛋白提供了配体,在神经胶质细胞引导的神经元迁移中起作用。

N-cadherin provides a and ligand for astrotactin that functions in glial-guided neuronal migration.

机构信息

Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065.

Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065

出版信息

Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):10556-10563. doi: 10.1073/pnas.1811100115. Epub 2018 Sep 27.

Abstract

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 in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronal , and more severe migration defects occurred after a conditional loss of glial 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, Thus, and bindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron-glial bridge complex that promotes glial-guided neuronal migration.

摘要

先前的研究表明,星状细胞黏附蛋白(ASTN1)为神经胶质导向的中枢神经系统迁移提供了神经元受体。在这里,我们报告 ASTN1 与 N 钙黏蛋白(CDH2)结合,并且 ASTN1:CDH2 相互作用支持细胞-细胞黏附。为了测试 ASTN1:CDH2 结合在神经胶质导向的神经元迁移中的功能,我们在小脑颗粒细胞和神经胶质中生成了条件性缺失 。在小脑切片培养物中,神经元 缺失后,颗粒细胞迁移速度减慢,而在神经胶质 缺失后,迁移缺陷更为严重。不与 CDH2 结合的 ASTN1 突变形式的颗粒细胞中的表达也减慢了迁移速度。此外,在缺少神经胶质而非神经元 的情况下,体外颗粒细胞和神经胶质嵌合体显示出神经元-神经胶质附着受损。因此,ASTN1 与神经元和神经胶质 CDH2 的 和 结合形成了一个不对称的神经元-神经胶质桥接复合物,促进了神经胶质导向的神经元迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07fc/6196552/540da7afc600/pnas.1811100115fig01.jpg

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