ADP Ribosylation Factor 6 Regulates Neuronal Migration in the Developing Cerebral Cortex through FIP3/Arfophilin-1-dependent Endosomal Trafficking of N-cadherin.
ADP Ribosylation Factor 6 Regulates Neuronal Migration in the Developing Cerebral Cortex through FIP3/Arfophilin-1-dependent Endosomal Trafficking of N-cadherin.
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DOI：
10.1523/eneuro.0148-16.2016
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发表时间：
2016-07
期刊：
影响因子：
3.4
通讯作者：
Sakagami H
中科院分区：
文献类型：
--
作者：
Hara Y;Fukaya M;Hayashi K;Kawauchi T;Nakajima K;Sakagami H
在神经发育过程中，内体运输通过与细胞-细胞和细胞-细胞外基质相互作用相关的膜蛋白的极化运输来控制细胞的形状和运动性。ADP核糖基化因子6（Arf 6）是一种重要的小GT3，其调节质膜和内体之间的膜运输。我们在此证明，敲低小鼠大脑皮质内源性Arf 6导致受损的中间区和迁移神经元中的N-钙粘蛋白和突触融合蛋白12的细胞质滞留的神经元迁移。与分离的功能Arf 6突变体的救援实验确定Rab 11家族相互作用蛋白3（FIP 3）/Arfophilin-1，Arf 6和Rab 11的双重效应，作为Arf 6在迁移神经元的下游效应。敲低FIP 3导致受损的神经元迁移的中间区和迁移神经元中的N-钙粘蛋白的胞质滞留，类似于Arf 6，这可以通过野生型FIP 3的共表达而不是缺乏Arf 6或Rab 11结合位点的FIP 3突变体来拯救。这些结果表明，Arf 6调节皮质神经元迁移的中间区通过FIP 3依赖的内体运输。
During neural development, endosomal trafficking controls cell shape and motility through the polarized transport of membrane proteins related to cell–cell and cell–extracellular matrix interactions. ADP ribosylation factor 6 (Arf6) is a critical small GTPase that regulates membrane trafficking between the plasma membrane and endosomes. We herein demonstrated that the knockdown of endogenous Arf6 in mouse cerebral cortices led to impaired neuronal migration in the intermediate zone and cytoplasmic retention of N-cadherin and syntaxin12 in migrating neurons. Rescue experiments with separation-of-function Arf6 mutants identified Rab11 family-interacting protein 3 (FIP3)/Arfophilin-1, a dual effector for Arf6 and Rab11, as a downstream effector of Arf6 in migrating neurons. The knockdown of FIP3 led to impaired neuronal migration in the intermediate zone and cytoplasmic retention of N-cadherin in migrating neurons, similar to that of Arf6, which could be rescued by the coexpression of wild-type FIP3 but not FIP3 mutants lacking the binding site for Arf6 or Rab11. These results suggest that Arf6 regulates cortical neuronal migration in the intermediate zone through the FIP3-dependent endosomal trafficking.