RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote Cortical Neuron Polarity.
RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote Cortical Neuron Polarity.
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DOI：
10.1016/j.celrep.2018.07.107
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发表时间：
2018-09-04
期刊：
影响因子：
8.8
通讯作者：
Pichaud F
中科院分区：
文献类型：
--
作者：
Mencarelli C;Nitarska J;Kroecher T;Ferraro F;Massey K;Riccio A;Pichaud F
发育中的皮层神经元极性开始于神经祖细胞向皮层板迁移的早期阶段，并随着轴突和树突的分化而达到高潮。在这里，我们表明，RAN依赖的核质运输机械是必不可少的皮层神经元极性的建立。我们发现，RAN结合蛋白1（RanBP 1）调节轴突规格和树突状分支在体外培养的神经元和放射状神经迁移在体内。在轴突发生过程中，RanBP 1调节极性蛋白LKB 1/Par 4的细胞质水平，这取决于核输出机制。我们的研究结果表明，RanBP 1的下游，LKB 1的功能是由STK 25-GM 130途径，促进通过高尔基体调节轴突发生介导的。我们的研究结果表明，核质运输机械是一个主要的调节神经元极性，包括径向迁移，并通过RanBP 1的出口LKB 1的调节是轴突生成的限制步骤。核质运输机制调节神经元极性Ran/RanBP 1调节轴突发生期间LKB 1的可用性Ran/RanBP 1耦合核质运输和高尔基体调节神经元如何获得其极性尚未完全了解。Mencarelli等人表明核质运输机制是神经元极性的关键调节器，包括径向迁移和轴突生成。他们设想，极性因子的核质转运可能是真核生物细胞极性的一般机制。
Neuronal polarity in the developing cortex begins during the early stages of neural progenitor migration toward the cortical plate and culminates with the specification of the axon and dendrites. Here, we demonstrate that the Ran-dependent nucleocytoplasmic transport machinery is essential for the establishment of cortical neuron polarity. We found that Ran-binding protein 1 (RanBP1) regulates axon specification and dendritic arborization in cultured neurons in vitro and radial neural migration in vivo. During axonogenesis, RanBP1 regulates the cytoplasmic levels of the polarity protein LKB1/Par4, and this is dependent on the nuclear export machinery. Our results show that downstream of RanBP1, LKB1 function is mediated by the STK25-GM130 pathway, which promotes axonogenesis through Golgi regulation. Our results indicate that the nucleocytoplasmic transport machinery is a main regulator of neuron polarity, including radial migration, and that the regulated export of LKB1 through RanBP1 is a limiting step of axonogenesis. The nucleocytoplasmic transport machinery regulates neuron polarity Ran/RanBP1 regulates LKB1 availability during axonogenesis Ran/RanBP1 couples nucleocytoplasmic transport and Golgi regulation How neurons acquire their polarity is not fully understood. Mencarelli et al. show that the nucleocytoplasmic transport machinery is a key regulator of neuron polarity, including radial migration and axonogenesis. They envisage that regulated nucleocytoplasmic transport of polarity factors may act as a general mechanism of cell polarity in eukaryotes.
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影响因子：
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作者：
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DOI：
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