Institut für Neurobiologie, Universität Münster, Münster, Germany.
Nat Neurosci. 2010 Nov;13(11):1357-64. doi: 10.1038/nn.2656. Epub 2010 Oct 3.
Interactions between neurons and glia are a key feature during the assembly of the nervous system. During development, glial cells often follow extending axons, implying that axonal outgrowth and glial migration are precisely coordinated. We found that the anaphase-promoting complex/cyclosome (APC/C) co-activator fizzy-related/Cdh1 (Fzr/Cdh1) is involved in the non-autonomous control of peripheral glial migration in postmitotic Drosophila neurons. APC/C(Fzr/Cdh1) is a cell-cycle regulator that targets proteins that are required for G1 arrest for ubiquitination and subsequent degradation. We found that Fzr/Cdh1 function is mediated by the immunoglobulin superfamily cell adhesion molecule Fasciclin2 (Fas2). In motor neurons Fzr/Cdh1 is crucial for the establishment of a graded axonal distribution of Fas2. Axonal Fas2 interacts homophilically with a glial isoform of Fas2. Glial migration is initiated along axonal segments that have low levels of Fas2 but stalls in axonal domains with high levels of Fas2 on their surfaces. This represents a simple mechanism by which a subcellular gradient of adhesiveness can coordinate glial migration with axonal growth.
神经元和神经胶质细胞之间的相互作用是神经系统组装过程中的一个关键特征。在发育过程中，神经胶质细胞通常会跟随延伸的轴突，这表明轴突的生长和神经胶质的迁移是精确协调的。我们发现，有丝分裂后期促进复合物/细胞周期蛋白（APC/C）共激活因子 fizzy-related/Cdh1（Fzr/Cdh1）参与了果蝇神经细胞有丝分裂后神经元中非自主控制周围神经胶质迁移的过程。APC/C（Fzr/Cdh1）是一种细胞周期调节剂，可靶向 G1 阻滞所需的蛋白质进行泛素化和随后的降解。我们发现 Fzr/Cdh1 的功能是通过免疫球蛋白超家族细胞粘附分子 Fasciclin2（Fas2）介导的。在运动神经元中，Fzr/Cdh1 对于 Fas2 的轴突分布梯度的建立是至关重要的。轴突 Fas2 与 Fas2 的一种神经胶质同工型发生同源相互作用。沿 Fas2 水平较低的轴突段开始发生神经胶质迁移，但在 Fas2 表面水平较高的轴突区域停滞。这代表了一种简单的机制，通过这种机制，细胞粘附的亚细胞梯度可以协调神经胶质迁移与轴突生长。
