RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development
RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development
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DOI：
10.1242/jcs.145037
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发表时间：
2014-02-01
影响因子：
4
通讯作者：
Lalli, Giovanna
中科院分区：
文献类型：
--
作者：
Das, Amlan;Gajendra, Sangeetha;Lalli, Giovanna
细胞极化对胚胎和出生后脑中的神经元发育都是必不可少的。在这里，使用原代培养，在体内出生后电穿孔和条件性基因消融，我们表明，Ras样的小GTdR RalA和它的效应器，外囊，调节形态和极化迁移的神经祖细胞来自脑室下区，一个主要的神经源性生态位在出生后的大脑。活性RalA通过非典型的PDZ结合基序促进外囊亚基Exo 84和Par 6的PDZ结构域之间的直接结合。阻断Exo 84-Par 6相互作用会损害出生后神经祖细胞和培养的胚胎神经元的极化。我们的研究结果提供了第一个在哺乳动物大脑中RalA功能的体内表征，并突出了细胞极化的一种新的分子机制。鉴于外囊和Par复合物在许多组织中是保守的，它们的相互作用的功能意义及其由RalA的调节在广泛的极化事件中可能是重要的。
Cell polarization is essential for neuronal development in both the embryonic and postnatal brain. Here, using primary cultures, in vivo postnatal electroporation and conditional genetic ablation, we show that the Ras-like small GTPase RalA and its effector, the exocyst, regulate the morphology and polarized migration of neural progenitors derived from the subventricular zone, a major neurogenic niche in the postnatal brain. Active RalA promotes the direct binding between the exocyst subunit Exo84 and the PDZ domain of Par6 through a non-canonical PDZ-binding motif. Blocking the Exo84-Par6 interaction impairs polarization in postnatal neural progenitors and cultured embryonic neurons. Our results provide the first in vivo characterization of RalA function in the mammalian brain and highlight a novel molecular mechanism for cell polarization. Given that the exocyst and the Par complex are conserved in many tissues, the functional significance of their interaction and its regulation by RalA are likely to be important in a wide range of polarization events.