KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development
KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development
复制标题
KASH 蛋白 Syne-2/Nesprin-2 和 SUN 蛋白 SUN1/2 在哺乳动物视网膜发育过程中介导核迁移。
DOI：
10.1093/hmg/ddq549
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发表时间：
2011-03-15
影响因子：
3.5
通讯作者：
Han, Min
中科院分区：
文献类型：
--
作者：
Yu, Juehua;Lei, Kai;Han, Min
在哺乳动物视网膜发育的某些阶段，细胞核相对于细胞体的运动是一个基本过程。在细胞分裂周期中光感受器细胞的产生过程中，祖细胞的细胞核在神经母细胞层（NBL）的顶端和基底表面之间振荡。这一过程被称为核往返移动（INM）。此外，新形成的光感受器细胞迁移并形成外核层（ONL）。在当前的研究中，我们证明了一种含KASH结构域的蛋白质，Syne - 2/Nesprin - 2，以及含SUN结构域的蛋白质，SUN1和SUN2，在小鼠视网膜的核往返移动和光感受器细胞迁移过程中发挥关键作用。Syne - 2/Nesprin - 2的缺失突变或Sun1和Sun2的双突变导致外核层厚度严重减小、光感受器细胞核定位错误以及视网膜出现严重的电生理功能障碍，其特征为a波和b波振幅降低。我们还提供证据表明，在视网膜中的细胞核迁移过程中，Syne - 2/Nesprin - 2在核膜处与SUN1或SUN2形成复合物，将细胞核与动力蛋白/动力蛋白激活蛋白和驱动蛋白分子马达连接起来。这些关键的视网膜发育信号结果将增进我们对哺乳动物视网膜中细胞核迁移机制的理解。
Nuclear movement relative to cell bodies is a fundamental process during certain aspects of mammalian retinal development. During the generation of photoreceptor cells in the cell division cycle, the nuclei of progenitors oscillate between the apical and basal surfaces of the neuroblastic layer (NBL). This process is termed interkinetic nuclear migration (INM). Furthermore, newly formed photoreceptor cells migrate and form the outer nuclear layer (ONL). In the current study, we demonstrated that a KASH domain-containing protein, Syne-2/Nesprin-2, as well as SUN domain-containing proteins, SUN1 and SUN2, play critical roles during INM and photoreceptor cell migration in the mouse retina. A deletion mutation of Syne-2/Nesprin-2 or double mutations of Sun1 and Sun2 caused severe reduction of the thickness of the ONL, mislocalization of photoreceptor nuclei and profound electrophysiological dysfunction of the retina characterized by a reduction of a-and b-wave amplitudes. We also provide evidence that Syne-2/Nesprin-2 forms complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus with dynein/dynactin and kinesin molecular motors during the nuclear migrations in the retina. These key retinal developmental signaling results will advance our understanding of the mechanism of nuclear migration in the mammalian retina.