2月9日，國(guó)際著名學(xué)術(shù)期刊《自然—細(xì)胞生物學(xué)》（Nature Cell Biology）在線發(fā)表了中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所研究員朱學(xué)良和美國(guó)華盛頓卡耐基研究所教授鄭詣先的合作研究結(jié)果：Nudel和胞質(zhì)動(dòng)力蛋白在紡錘體基質(zhì)組裝中發(fā)揮重要作用,，進(jìn)而調(diào)控有絲分裂紡錘體的正確形成,。
紡錘體是主要由微管形成的紡錘形的動(dòng)態(tài)結(jié)構(gòu)，負(fù)責(zé)真核細(xì)胞有絲分裂過(guò)程中遺傳物質(zhì)（染色體）的均等分離,。因此,，紡錘體的異常會(huì)引起遺傳不穩(wěn)定，從而導(dǎo)致細(xì)胞死亡或腫瘤,、癌癥等疾病的發(fā)生,。早在幾十年前，人們就提出可能存在一些獨(dú)立于微管的基質(zhì)成分,，對(duì)紡錘體組裝起著重要作用,，但一直未能被證實(shí)。鄭詣先研究組近來(lái)利用偶聯(lián)有蛋白質(zhì)激酶Aurora A的微小磁珠在非洲爪蟾卵抽提物中組裝成的紡錘體,，證明了一種富含生物膜的紡錘體基質(zhì)（spindle matrix）的存在,，并發(fā)現(xiàn)B型核纖層蛋白（Lamin）也是其中的一個(gè)重要成分。這種紡錘體基質(zhì)與微管相輔相成,，前者促進(jìn)后者形成正常的紡錘體結(jié)構(gòu),，而后者的聚合又增強(qiáng)前者的組裝。另一方面,，紡錘體的正確形成需要胞質(zhì)動(dòng)力蛋白（dynein）,，即一種被稱(chēng)作“分子馬達(dá)”的能夠朝向微管負(fù)端運(yùn)動(dòng)的蛋白質(zhì)復(fù)合物。朱學(xué)良研究小組發(fā)現(xiàn),，Nudel是dynein的調(diào)節(jié)因子,，并在有絲分裂中有重要功能。
作為中科院“海外合作伙伴計(jì)劃”的成員,，他們共同探索了紡錘體組裝的機(jī)理,。博士研究生馬麗觀察到體外紡錘體形成過(guò)程中微管和基質(zhì)的詳細(xì)變化，發(fā)現(xiàn)微管首先從Aurora A磁珠上長(zhǎng)出,，形成放射狀的星體（aster）,，同時(shí)在微管上出現(xiàn)含Lamin B的顆粒；隨著時(shí)間的推移,，星體微管密度加大但長(zhǎng)度變短,，形成球狀物，在此過(guò)程中,，兩個(gè)星體會(huì)融合形成以磁珠為兩極的紡錘體,，Lamin B的顆粒也變得高度富集,。她和同事們發(fā)現(xiàn)，分離出的紡錘體基質(zhì)中含有dynein和Nudel,，并且Lamin B可以和Nudel直接結(jié)合,。去除Nudel或失活dynein，都可以抑制基質(zhì)的富集并使紡錘體組裝停留在星體階段,。去除Lamin B后,，則形成膨大的異常紡錘體。這些結(jié)果說(shuō)明,，Nudel和dynein可以通過(guò)聚集Lamin B等紡錘體基質(zhì)成分來(lái)調(diào)節(jié)紡錘體的組裝,。而且，由于分離的紡錘體基質(zhì)中還含有大量參與細(xì)胞信號(hào)轉(zhuǎn)導(dǎo),、轉(zhuǎn)錄調(diào)控,、膜運(yùn)輸?shù)裙δ艿闹匾鞍踪|(zhì)分子，研究人員推測(cè),，紡錘體基質(zhì)可能還行使其他有待進(jìn)一步認(rèn)識(shí)的功能,。
這項(xiàng)研究得到了科技部、國(guó)家自然科學(xué)基金委,、中國(guó)科學(xué)院以及美國(guó)霍華德休斯醫(yī)學(xué)院,、美國(guó)卡耐基研究所的經(jīng)費(fèi)支持。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology (08 Feb 2009), doi: 10.1038/ncb1832
Requirement for Nudel and dynein for assembly of the lamin B spindle matrix
Li Ma1,2, Ming-Ying Tsai2,3, Shusheng Wang2, Bingwen Lu4, Rong Chen2, John R. Yates III4, Xueliang Zhu1 & Yixian Zheng1,2
The small guanosine triphosphatase Ran loaded with GTP (RanGTP) can stimulate assembly of the type V intermediate filament protein lamin B into a membranous lamin B spindle matrix, which is required for proper microtubule organization during spindle assembly. Microtubules in turn enhance assembly of the matrix. Here we report that the isolated matrix contains known spindle assembly factors such as dynein and Nudel. Using spindle assembly assays in Xenopus egg extracts, we show that Nudel regulates microtubule organization during spindle assembly independently of its function at kinetochores. Importantly, Nudel interacts directly with lamin B to facilitate the accumulation and assembly of lamin-B-containing matrix on microtubules in a dynein-dependent manner. Perturbing either Nudel or dynein inhibited the assembly of lamin B matrix. However, depleting lamin B still allowed the formation of matrices containing dynein and Nudel. Therefore, dynein and Nudel regulate assembly of the lamin B matrix. Interestingly, we found that whereas depleting lamin B resulted in disorganized spindle and spindle poles, disrupting the function of Nudel or dynein caused a complete lack of spindle pole focusing. We suggest that Nudel regulates microtubule organization in part by facilitating assembly of the lamin B spindle matrix in a dynein-dependent manner
1 Laboratory of Molecular Cell Biology and Center of Cell Signaling, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
2 Department of Embryology, Carnegie Institution for Science and Howard Hughes Medical Institute, Baltimore, Maryland 21218, USA.
3 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
4 Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
