中科院神经科学研究所所长蒲慕明主要研究的方向包括神经环路的可塑性,从神经可塑性到大脑的发育。近期其国外研究团队又获得了重要研究进展。
研究发现分泌性导向因子的细胞外梯度(Extracellular gradients)能帮助引导轴突和神经细胞迁移,这些因子都是结合在细胞表面或者细胞外基质上的,但是至今科学家们还不清楚这些因子是否,以及如何利用梯度作用的。
在这篇文章中,研究人员发展了一种新技术,能快速获得底物结合蛋白的显微梯度(microscopic gradients),利用这种方法,研究人员获得了新的研究成果,提出底物结合导向因子能高效极化轴突的生成和生长,并且这种技术还能用于研究结合蛋白导向诱导的神经元应答。(生物谷Bioon.com)
生物谷推荐原始出处:
The Journal of Neuroscience, June 10, 2009, 29(23):7450-7458; doi:10.1523/JNEUROSCI.1121-09.2009
Axon Initiation and Growth Cone Turning on Bound Protein Gradients
Junyu Mai,1 Lee Fok,1 Hongfeng Gao,2 Xiang Zhang,1,3 and Mu-ming Poo2
1National Science Foundation Nano-Scale Science and Engineering Center and 2Department of Molecular and Cell Biology, University of California, Berkeley, and 3Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720
Extracellular gradients of secreted guidance factors are known to guide axon pathfinding and neuronal migration. These factors are likely to bind to cell surfaces or extracellular matrix, but whether and how they may act in bound gradients remains mostly unclear. In this study, we have developed a new technique for rapid production of stable microscopic gradients of substrate-bound proteins by covalent bonding of the proteins with an epoxy-coated glass substrate while they are diffusing in an agarose gel. Using this method, we found that bound gradients of netrin-1 and brain-derived neurotrophic factor (BDNF) can polarize the initiation and turning of axons in cultured hippocampal neurons. Furthermore, bound BDNF gradient caused attractive and repulsive polarizing response on gradients of low- and high-average density of BDNF, respectively. This novel bidirectional response to BDNF depended on the basal level of cAMP in the neuron. Finally, our data showed that the neuron's attractive response to bound BDNF gradient depended on the absolute difference rather than the relative difference in the BDNF density across the neuron, with a minimal effective difference of 1–2 BDNF molecule/μm2 on the substrate surface. Thus, substrate-bound guidance factors are highly effective in polarizing axon initiation and growth, and the diffusive printing technique is useful for studying neuronal responses induced by bound protein gradients.