來自復(fù)旦大學(xué)生科院發(fā)育生物學(xué)與分子醫(yī)學(xué)研究院,，杜克大學(xué)醫(yī)學(xué)中心,，耶魯大學(xué)醫(yī)學(xué)院的研究人員的一項(xiàng)新成果填補(bǔ)了神經(jīng)細(xì)胞遷移機(jī)制中的一個(gè)重要空白：發(fā)現(xiàn)SUN結(jié)構(gòu)域和KASH結(jié)構(gòu)域蛋白在細(xì)胞核移動(dòng)方面的重要作用,，這為細(xì)胞遷移研究提供了重要信息,。這一研究成果公布在Neuron雜志上,。
SUN1蛋白是哺乳動(dòng)物中發(fā)現(xiàn)的第一個(gè)與生殖細(xì)胞形成有關(guān)的內(nèi)核膜蛋白，也是首次發(fā)現(xiàn)SUN1蛋白在哺乳動(dòng)物配子形成過程中發(fā)揮重要作用,。SUN1基因突變小鼠也是哺乳動(dòng)物中建立的第一例研究染色體端粒動(dòng)態(tài)變化與減數(shù)分裂進(jìn)程的動(dòng)物模型,。
韓珉博士研究組一直以來都在從事SUN蛋白的研究，之前他們發(fā)現(xiàn)SUN1蛋白是將染色體端粒定位在核膜上進(jìn)而進(jìn)行配對的“橋梁”,，對生殖細(xì)胞形成具有相當(dāng)關(guān)鍵的作用,。一旦SUN1基因突變，不再具有“橋梁”作用,，其后果就是造成染色體配對和遺傳重組受阻,。復(fù)旦科研人員發(fā)現(xiàn)，SUN1基因敲除的突變體小鼠是不育的,，主要原因是由于突變體小鼠中,，端粒不能定位于核膜上，造成精母細(xì)胞和卵母細(xì)胞內(nèi)的同源染色體配對,、聯(lián)會和重組嚴(yán)重受阻,。這從遺傳學(xué)角度解開了不育癥形成的一個(gè)新原因，對于不育癥的診斷提供了新的線索,。
最新的這篇文章則發(fā)現(xiàn)了SUN蛋白在神經(jīng)細(xì)胞遷移方面的作用,。神經(jīng)細(xì)胞遷移的分子水平機(jī)制是現(xiàn)代發(fā)育神經(jīng)生物學(xué)的一個(gè)重要課題。從80年代起,，有多個(gè)實(shí)驗(yàn)室從不同角度對神經(jīng)細(xì)胞遷移進(jìn)行了分子水平的研究,。
研究人員發(fā)現(xiàn)了兩個(gè)SUN結(jié)構(gòu)域蛋白：SUN1和SUN2，以及兩個(gè)KASH結(jié)構(gòu)域蛋白：Syne-1和Syne-2在這個(gè)過程中得重要作用：幫助連接中心粒和細(xì)胞核,。而且研究人員還發(fā)現(xiàn)SUN1和SUN2能幫助聚集Syne-2道細(xì)胞核膜上,，與膜錨定dynein蛋白形成復(fù)合物。
另外研究人員也發(fā)現(xiàn)缺失Syne-2蛋白的小鼠會出現(xiàn)嚴(yán)重的認(rèn)知和記憶方面的缺陷,，這說明SUN結(jié)構(gòu)域和KASH結(jié)構(gòu)域蛋白在細(xì)胞核移動(dòng)方面的重要作用,，這也填補(bǔ)了我們對于神經(jīng)細(xì)胞遷移認(rèn)識的一個(gè)重要空白。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron, Volume 64, Issue 2, 173-187, 29 October 2009 doi:10.1016/j.neuron.2009.08.018
SUN1/2 and Syne/Nesprin-1/2 Complexes Connect Centrosome to the Nucleus during Neurogenesis and Neuronal Migration in Mice
Xiaochang Zhang1, Kai Lei1, Xiaobing Yuan2, Xiaohui Wu1, Yuan Zhuang1, 3, Tian Xu1, 4, Rener Xu1, , and Min Han1, 5, ,
1 Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai 200433, China
2 Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3 Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
4 Howard Hughes Medical Institute and Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA
5 Howard Hughes Medical Institute and Department of MCDB, University of Colorado, Boulder, CO 80309, USA
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 SUN1 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 SUN1 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.
