Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065.
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065
Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):10556-10563. doi: 10.1073/pnas.1811100115. Epub 2018 Sep 27.
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.
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。
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