JIP1 Mediates Anterograde Transport of Rab10 Cargos during Neuronal Polarization
JIP1 Mediates Anterograde Transport of Rab10 Cargos during Neuronal Polarization
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DOI：
10.1523/jneurosci.4496-13.2014
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发表时间：
2014-01-29
影响因子：
5.3
通讯作者：
Luo, Zhen-Ge
中科院分区：
文献类型：
--
作者：
Deng, Cai-Yun;Lei, Wen-Liang;Luo, Zhen-Ge
轴突的发育和伸长需要严格控制的新膜添加。在此之前，我们已经表明Rab 10参与定向质膜前体囊泡（PPV）在神经元极化和轴突生长过程中的膜插入。然而，负责PPV运输的机制仍不清楚。在这里，我们发现c-Jun N-末端激酶相互作用蛋白1（JIP 1）与GTP锁定的Rab 10活性形式相互作用，并直接将Rab 10连接到驱动蛋白1轻链（KLC）。驱动蛋白1/JIP 1/Rab 10复合物是PPV在轴突生长过程中顺行运输所必需的。下调JIP 1或KLC或破坏这种复合物的形成减少了PPV在发育中的轴突中的顺行运输，并导致神经元极性缺陷。此外，该复合物在体内大鼠新皮层神经元极化中起重要作用。因此，这项研究已经证明了轴突发育中涉及的定向膜运输的机制。
Axon development and elongation require strictly controlled new membrane addition. Previously, we have shown the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles (PPVs) during neuronal polarization and axonal growth. However, the mechanism responsible for PPV transportation remains unclear. Here we show that c-Jun N-terminal kinase-interacting protein 1 (JIP1) interacts with GTP-locked active form of Rab10 and directly connects Rab10 to kinesin-1 light chain (KLC). The kinesin-1/JIP1/Rab10 complex is required for anterograde transport of PPVs during axonal growth. Downregulation of JIP1 or KLC or disrupting the formation of this complex reduces anterograde transport of PPVs in developing axons and causes neuronal polarity defect. Furthermore, this complex plays an important role in neocortical neuronal polarization of rats in vivo. Thus, this study has demonstrated a mechanism underlying directional membrane trafficking involved in axon development.