生物谷報道：最近,，科學(xué)家發(fā)現(xiàn)一個被稱為肌球蛋白X的動力蛋白在神經(jīng)元的生長過程中起著主要作用，在它的幫助下,，神經(jīng)元細(xì)胞將通過末梢突觸而連接起來,。佐治亞醫(yī)學(xué)院神經(jīng)生物學(xué)家Wen-Cheng Xiong（熊文成）教授介紹說，在關(guān)于神經(jīng)元之間怎樣形成連接的各種困惑中,，研究者發(fā)現(xiàn)肌球蛋白X可在稱為肌纖蛋白絲的神經(jīng)元軸突上移動,，這種肌纖蛋白絲可看作是神經(jīng)元細(xì)胞中極高速傳導(dǎo)區(qū)域中的“雙向高速公路”。
Xiong教授和她的同事們在1月21號細(xì)胞生物學(xué)網(wǎng)及2月出版的《自然細(xì)胞生物學(xué)》雜志上報道說,在中央核綜合處理后肌球蛋白X承載著結(jié)腸直腸癌（DCC）受體移動至神經(jīng)元末梢,。在那里,，DCC受體和神經(jīng)生長因子-1共同作用，對名為軸突的神經(jīng)元細(xì)胞橫向生長起指導(dǎo)作用,，以確保其生長方向正確,。最終單個神經(jīng)元細(xì)胞之間通過末端突觸相互聯(lián)系起來。Xiong教授介紹說：“在神經(jīng)元細(xì)胞早期發(fā)育過程中,，軸突的生長需要確定目標(biāo),，即生長長度及生長方向，而最終它們將形成神經(jīng)通路”,， 她曾經(jīng)仔細(xì)分析過神經(jīng)元細(xì)胞在脊髓損傷及其他病癥中是怎樣在短時間內(nèi)幫助其恢復(fù)聯(lián)系的,。“神經(jīng)元的生長發(fā)育過程被精確的控制著，”一旦發(fā)生錯誤將會影響整個大腦神經(jīng)元的構(gòu)建或連接,，“肌球蛋白X承載著DCC受體到需要和神經(jīng)生長因子-1共同作用的地方,。”
Xiong教授先前發(fā)表在2004年《自然神經(jīng)科學(xué)》雜志上的研究表明，當(dāng)DCC受體和神經(jīng)生長因子-1結(jié)合后,，激活了一種黏著斑激酶（FAK）,，促使發(fā)育中的神經(jīng)元細(xì)胞沿著明確的方向生長延伸,。在這個過程中神經(jīng)元細(xì)胞間彼此形成了聯(lián)系，最終使發(fā)育中的大腦和脊髓形成了連接,。當(dāng)這個激酶被去除后,，軸突生長將會失去正常的連接。當(dāng)研究者們阻斷了肌球蛋白X的移動時,，軸突生長受到了妨礙，研究者認(rèn)為在脊髓神經(jīng)損傷時同樣存在這種情況,。Xiong教授認(rèn)為：“肌球蛋白X在神經(jīng)生長發(fā)育過程中起著關(guān)鍵作用”,。
Figure 2. Regulation of DCC distribution in neurons by Myo X.
(a) DCC redistribution in neurons expressing Myo X. Rat cortical neurons (E17, DIV 3) transfected with indicated GFP or GFP–Myo X plasmids were fixed and stained with antibodies against DCC for endogenous DCC distribution (red). GFP (green) indicated expression of GFP or GFP-fused Myo X proteins. The square boxes were magnified and are shown in the inserts. DCC–Myo X colocalizing puncta were indicated by filled arrows and the non-colocalized Myo X puncta were indicated by open arrows. (b, c) Quantification of data from a. In b, the percentage of GFP–Myo X and GFP–Myo X Tail puncta that colocalized with the endogenous DCC are presented as means s.e.m. (n = 3). The asterisk indicates P <0.01, in comparison with cells expressing GFP–Myo X. In c, the ratio of DCC immunofluorescence intensity in neurites over soma are presented as means s.e.m. (n = 10). The asterisk indicates P <0.01, in comparison with cells expressing GFP alone. (d) Reduced DCC distribution in neurites by suppression of Myo X expression. Rat cortical neurons (E17, DIV 7) transfected with control miRNA (scramble miRNA) or Myo X miRNA were fixed and stained with antibodies against DCC for endogenous DCC distribution (red). GFP indicates expression of transfected miRNA plasmids. The boxed areas were magnified and are shown in the right-hand panels. Transfected neurons are indicated by filled arrows and untransfected neurons are indicated by open arrows. (e) Quantification of data from d. The ratio of DCC immunoflourescence intensity in neurites over soma are presented as means s.e.m. (n = 10). The asterisk indicates P <0.01, in comparison with neurons expressing scramble miRNA. The scale bars represent 50 m in a and d.
原文出處：
Myosin X regulates netrin receptors and functions in axonal path-finding
Xiao-Juan Zhu, Cheng-Zhong Wang, Peng-Gao Dai, Yi Xie, Ning-Ning Song, Yu Liu, Quan-Sheng Du, Lin Mei, Yu-Qiang Ding & Wen-Cheng Xiong
Published online: 21 January 2007 | doi:10.1038/ncb1535
Abstract | Full text | PDF (2,585K) | Supplementary Information
作者簡介：
Wen-Cheng Xiong, M.D. PhD
Research Emphasis:
Neurons migrate and extend axons and dendrites to build the nerve network in the brain. Osteoclasts attach to the bone matrix to absorb and remodel bones. Cancer cells migrate to cause tumor metastasis. These processes all require engagement of cells with the extracellular matrix which activates integrin signaling and regulates actin cytoskeleton reorganization. Cells at the same time integrate pathways in response to diffusible environmental cues to mediate a variety of activities including cell adhesion and migration. We are interested in how signals are propagated from the cell surface to cytoskeleton to mediate cell migration. A combination of molecular, cell biological, and genetic approaches has been employed to address this question.
Selected Publications
Wong, K.,. Ren, X.R.,. Huang, Y-Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S., Mei, L.,. Wu, J. Y., Xiong, W-C., and. Rao, Y. Signaling transduction in neuronal migration: roles of RhoGTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. (2001) Cell 107: 209-221.
Wang, Q., Xie, Y., Du, Q-S., Wu, X-J., Feng, X.,. Mei,, L., McDonald, J., and Xiong, W-C. (2003) Regulation of the formation of osteoclastic actin rings by PYK2 interacting with gelsolin. J. Cell Biol. 160: 565-575.
Ren, X.R., Ming, G-L., Xie, Y., Hong, Y., Sun, D-M., Zhao, Z-q., Feng, Z., Wang, Q., Shim, S., Chen, Z-f., Song, H-j., Mei, L., and Xiong, W.C.(2004) Focal adhesion kinase in Netrin-1 signaling. Nature Neurosci. in press
相關(guān)基因：
MYO10
Official Symbol: MYO10 and Name: myosin X [Homo sapiens]
Other Aliases: FLJ10639, FLJ21066, FLJ22268, FLJ43256, KIAA0799, MGC131988
Chromosome: 5; Location: 5p15.1-p14.3
MIM: 601481
GeneID: 4651
NTN1
Official Symbol: NTN1 and Name: netrin 1 [Homo sapiens]
Other Aliases: NTN1L
Other Designations: netrin 1, mouse, homolog of
Chromosome: 17; Location: 17p13-p12
MIM: 601614
GeneID: 9423
