中科院神經(jīng)科學(xué)研究所所長蒲慕明主要研究的方向包括神經(jīng)環(huán)路的可塑性,,從神經(jīng)可塑性到大腦的發(fā)育。近期其國外研究團隊又獲得了重要研究進展,。
研究發(fā)現(xiàn)分泌性導(dǎo)向因子的細胞外梯度(Extracellular gradients)能幫助引導(dǎo)軸突和神經(jīng)細胞遷移,,這些因子都是結(jié)合在細胞表面或者細胞外基質(zhì)上的,但是至今科學(xué)家們還不清楚這些因子是否,,以及如何利用梯度作用的。
在這篇文章中,,研究人員發(fā)展了一種新技術(shù),,能快速獲得底物結(jié)合蛋白的顯微梯度(microscopic gradients),利用這種方法,,研究人員獲得了新的研究成果,,提出底物結(jié)合導(dǎo)向因子能高效極化軸突的生成和生長,并且這種技術(shù)還能用于研究結(jié)合蛋白導(dǎo)向誘導(dǎo)的神經(jīng)元應(yīng)答,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.