RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex.
RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex.
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RAB18 是一种与 Warburg Micro 综合征相关的蛋白质，控制发育中的大脑皮层中的神经元迁移
DOI：
10.1186/s13041-016-0198-2
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发表时间：
2016-02-16
期刊：
影响因子：
3.6
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Wu Q;Sun X;Yue W;Lu T;Ruan Y;Chen T;Zhang D
RAB18的功能突变缺失已在人类神经和发育障碍Warburg Micro综合征患者中被发现。然而，RAB18在脑中的功能尚不清楚。在本研究中，我们报道RAB18是神经元迁移和形态发生的关键调节因子。在子宫内电穿孔抑制小鼠脑内RAB18损伤径向迁移。RAB18显性阴性的过表达或RAB3GAP （RAB18GEF）的破坏也会导致发育中的小鼠皮层神经元迁移延迟，并在体外抑制神经突生长。此外，RAB18的缺失诱导N-cadherin通过溶酶体途径加速降解，导致神经元上N-cadherin表面水平降低。RAB18调控发育过程中神经元的迁移和形态发生。我们的研究结果强调了RAB3GAP-RAB18通路在大脑皮层发育中的关键作用，并可能解释Warburg Micro综合征患者观察到的一些临床特征。本文的在线版本（doi:10.1186/s13041-016-0198-2）包含补充材料，仅供授权用户使用。
Loss of function mutations in RAB18, has been identified in patients with the human neurological and developmental disorder Warburg Micro syndrome. However, the function of RAB18 in brain remains unknown. In this study, we report that RAB18 is a critical regulator of neuronal migration and morphogenesis. Using in utero electroporation suppression of RAB18 in the mouse brain impairs radial migration. Overexpression of dominant negative RAB18 or disruption of RAB3GAP (RAB18GEF) also results in delayed neuronal migration in the developing mouse cortex and inhibition of neurite growth in vitro. Moreover, loss of RAB18 induces an acceleration of N-cadherin degradation by lysosomal pathway resulting in the decrease of surface level of N-cadherin on neurons. RAB18 regulates neuronal migration and morphogenesis during development. Our findings highlight the critical role of RAB3GAP-RAB18 pathway in the developing cerebral cortex and might explain some of clinical features observed in patients with Warburg Micro syndrome. The online version of this article (doi:10.1186/s13041-016-0198-2) contains supplementary material, which is available to authorized users.