生物谷报道:最近,科学家发现一个被称为肌球蛋白X的动力蛋白在神经元的生长过程中起着主要作用,在它的帮助下,神经元细胞将通过末梢突触而连接起来。佐治亚医学院神经生物学家Wen-Cheng Xiong(熊文成)教授介绍说,在关于神经元之间怎样形成连接的各种困惑中,研究者发现肌球蛋白X可在称为肌纤蛋白丝的神经元轴突上移动,这种肌纤蛋白丝可看作是神经元细胞中极高速传导区域中的“双向高速公路”。
Xiong教授和她的同事们在1月21号细胞生物学网及2月出版的《自然细胞生物学》杂志上报道说,在中央核综合处理后肌球蛋白X承载着结肠直肠癌(DCC)受体移动至神经元末梢。在那里,DCC受体和神经生长因子-1共同作用,对名为轴突的神经元细胞横向生长起指导作用,以确保其生长方向正确。最终单个神经元细胞之间通过末端突触相互联系起来。Xiong教授介绍说:“在神经元细胞早期发育过程中,轴突的生长需要确定目标,即生长长度及生长方向,而最终它们将形成神经通路”, 她曾经仔细分析过神经元细胞在脊髓损伤及其他病症中是怎样在短时间内帮助其恢复联系的。“神经元的生长发育过程被精确的控制着,”一旦发生错误将会影响整个大脑神经元的构建或连接,“肌球蛋白X承载着DCC受体到需要和神经生长因子-1共同作用的地方。”
Xiong教授先前发表在2004年《自然神经科学》杂志上的研究表明,当DCC受体和神经生长因子-1结合后,激活了一种黏着斑激酶(FAK),促使发育中的神经元细胞沿着明确的方向生长延伸。在这个过程中神经元细胞间彼此形成了联系,最终使发育中的大脑和脊髓形成了连接。当这个激酶被去除后,轴突生长将会失去正常的连接。当研究者们阻断了肌球蛋白X的移动时,轴突生长受到了妨碍,研究者认为在脊髓神经损伤时同样存在这种情况。Xiong教授认为:“肌球蛋白X在神经生长发育过程中起着关键作用”。
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.
原文出处:
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
作者简介:
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
相关基因:
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