日本奈良尖端科学技术大学院大学日前发表公报称,该机构研究人员在动物实验中,弄清了神经细胞在生长过程中出现非对称形状的详细机制,这一发现将有助于开发恢复受损神经的新治疗方法。
神经细胞本来呈球状,但是在生长过程中,会伸出3至6个左右的突起,其中一个突起会变长,成为轴突。轴突主要作用是连接其他神经细胞,从而使神经细胞间可以传递信息。
通过培养老鼠脑内的海马体神经细胞,研究人员发现,在海马体神经细胞本体和突起间往来移动的“SHOOTIN”蛋白质对于破坏神经细胞的对称性发挥了重要作用。此外,如果一个突起的“SHOOTIN”蛋白质的量比其他突起多,那么这个突起就会伸长,最终成长为轴突。
公报说,研究人员今后可研究利用“SHOOTIN”蛋白质,对脊髓损伤等神经损伤类患者进行治疗,延长他们的神经细胞轴突,从而重新准确连接受损或被切断的神经。
有关研究成果已发表在新一期英国《分子系统生物学》杂志网络版上。(生物谷Bioon.com)
生物谷推荐原文出处:
Molecular Systems Biology doi:10.1038/msb.2010.51
A diffusion-based neurite length-sensing mechanism involved in neuronal symmetry breaking
Michinori Toriyama1, Yuichi Sakumura2,3, Tadayuki Shimada1, Shin Ishii2,3,4,5 & Naoyuki Inagaki1,3
1Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan
2Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Japan
3Institute for Bioinformatics Research and Development, Japan Science and Technology Agency (JST), Tokyo, Japan
4Graduate School of Informatics, Kyoto University, Uji, Japan
5Computational Science Research Program, RIKEN, Saitama, Japan
Although there has been significant progress in understanding the molecular signals that change cell morphology, mechanisms that cells use to monitor their size and length to regulate their morphology remain elusive. Previous studies suggest that polarizing cultured hippocampal neurons can sense neurite length, identify the longest neurite, and induce its subsequent outgrowth for axonogenesis. We observed that shootin1, a key regulator of axon outgrowth and neuronal polarization, accumulates in neurite tips in a neurite length-dependent manner; here, the property of cell length is translated into shootin1 signals. Quantitative live cell imaging combined with modeling analyses revealed that intraneuritic anterograde transport and retrograde diffusion of shootin1 account for its neurite length-dependent accumulation. Our quantitative model further explains that the length-dependent shootin1 accumulation, together with shootin1-dependent neurite outgrowth, constitutes a positive feedback loop that amplifies stochastic fluctuations of shootin1 signals, thereby generating an asymmetric signal for axon specification and neuronal symmetry breaking.