SUN1/2 and Syne/Nesprin-1/2 Complexes Connect Centrosome to the Nucleus during Neurogenesis and Neuronal Migration in Mice

被引：365

作者：

Zhang, Xiaochang ^{[1
]}

Lei, Kai ^{[1
]}

Yuan, Xiaobing ^{[2
,3
]}

Wu, Xiaohui ^{[1
]}

Zhuang, Yuan ^{[1
,4
]}

Xu, Tian ^{[1
,5
,6
]}

Xu, Rener ^{[1
]}

Han, Min ^{[1
,7
,8
]}

机构：

[1] Fudan Univ, Sch Life Sci, Inst Dev Biol & Mol Med, Shanghai 200433, Peoples R China

[2] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Neurobiol, Shanghai 200031, Peoples R China

[4] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA

[5] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA

[6] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA

[7] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA

[8] Univ Colorado, Dept MCDB, Boulder, CO 80309 USA

来源：

NEURON | 2009年 / 64卷 / 02期

基金：

中国国家自然科学基金;

关键词：

MEMBRANE PROTEIN; LIS1; ENVELOPE; DYNEIN; LAMIN; ANCHORAGE; NESPRIN-2; ROLES; LOCALIZATION; MECHANISMS;

D O I：

10.1016/j.neuron.2009.08.018

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：173 / 187

页数：15

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