SUN1/2 and Syne/Nesprin-1/2 Complexes Connect Centrosome to the Nucleus during Neurogenesis and Neuronal Migration in Mice
SUN1/2 and Syne/Nesprin-1/2 Complexes Connect Centrosome to the Nucleus during Neurogenesis and Neuronal Migration in Mice
复制标题
SUN1/2 和 Syne/Nesprin-1/2 复合物在小鼠神经发生和神经元迁移过程中将中心体连接到细胞核
DOI：
10.1016/j.neuron.2009.08.018
复制
发表时间：
2009-10-29
期刊：
影响因子：
16.2
通讯作者：
Han, Min
中科院分区：
文献类型：
--
作者：
Zhang, Xiaochang;Lei, Kai;Han, Min
核运动在神经发生和神经元迁移过程中至关重要，这是哺乳动物大脑发育的基础。虽然dynein、Lis1和其他细胞质蛋白因其在核互动迁移（INM）和核分裂过程中将微管连接到细胞核而闻名，但将dynein/Lis1连接到核膜（NE）的因素仍有待确定。我们在这里报道了太阳结构域蛋白SUM和SUN2以及kash结构域蛋白Syne-1/ nesprin1和Syne-2/ nesprin2在小鼠神经发生和神经元迁移中起关键作用。我们发现SUM和SUN2与Syne-2形成冗余复合物，在大脑皮层的INM和径向神经元迁移过程中介导中心体-核耦合。syn2通过与动力蛋白/动力蛋白和动力蛋白复合物的相互作用连接到中心体。Syne-2突变体在学习和记忆方面也表现出严重缺陷。这些结果令人满意。这是我们对大脑发育过程中核运动机制理解的一个重要空白。
Nuclear movement is critical during neurogenesis and neuronal migration, which are fundamental for mammalian brain development. Although dynein, Lis1, and other cytoplasmic proteins are known for their roles in connecting microtubules to the nucleus during interkinetic nuclear migration (INM) and nucleokinesis, the factors connecting dynein/Lis1 to the nuclear envelope (NE) remain to be determined. We report here that the SUN-domain proteins SUM and SUN2 and the KASH-domain proteins Syne-1/Nesprin-1 and Syne-2/Nesprin-2 play critical roles in neurogenesis and neuronal migration in mice. We show that SUM and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. Syne-2 is connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes. Syne-2 mutants also display severe defects in learning and memory. These results fill. an important gap in our understanding of the mechanism of nuclear movement during brain development.