中科院神经所蒲慕明和段树民带领的研究团队在新一期Cell发表了有关神经元蛋白极性分布机制的最新研究论文。
神经元是一种极性细胞,以轴突的起始段为界,可分为轴突和胞体树突两大部分。树突负责接收信息,轴突则负责输出信息。这种不对称的功能,依赖于不同功能的蛋白在轴突和树突上的不对称分布。神经元蛋白的极性分布如何形成以及维持,是神经生物学领域的重要问题。
来自神经所的报道称,研究小组发现在接近胞体的轴突起始段(AIS)存在一个由肌动蛋白和Ankyrin G构成的分子筛,像滤网一样限制了大分子蛋白在轴突和胞体之间的扩散,但允许某些依赖特定马达蛋白转运的膜蛋白通过。
进一步的研究发现,马达蛋白驱动力的强弱,以及膜蛋白-马达蛋白复合体运输效能的高低,是膜蛋白能否通过AIS分子筛的决定条件。轴突膜蛋白转运复合体VAMP2-KIF5的运输效能较高,可以穿过分子筛从胞体转运到轴突内,而树突膜蛋白转运复合体NR2B-KIF17和GluR2-KIF5的运输效能较低,不能穿越这个胞浆屏障。这一新颖的机制,为研究神经元蛋白的极性分布提供了崭新的角度,具有重要的理论意义。(生物谷Bioon.com)
生物谷推荐原始出处:
Cell, 05 March 2009 doi:10.1016/j.cell.2009.01.016
A Selective Filter for Cytoplasmic Transport at the Axon Initial Segment
Ai-hong Song1,Dong Wang1,Gang Chen1,Yuju Li1,Jianhong Luo2,Shumin Duan1,,andMu-ming Poo1,3,,
1 Institute of Neuroscience, State Key Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2 Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310031, China
3 Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720-3200, USA
Summary
Distinct molecules are segregated into somatodendritic and axonal compartments of polarized neurons, but mechanisms underlying the development and maintenance of such segregation remain largely unclear. In cultured hippocampal neurons, we observed an ankyrin G- and F-actin-dependent structure that emerged in the cytoplasm of the axon initial segment (AIS) within 2 days after axon/dendrite differentiation, imposing a selective filter for diffusion of macromolecules and transport of vesicular carriers into the axon. Axonal entry was allowed for KIF5-driven carriers of synaptic vesicle protein VAMP2, but not for KIF17-driven carriers of dendrite-targeting NMDA receptor subunit NR2B. Comparisons of transport rates between chimeric forms of KIF17 and KIF5B, with the motor and cargo-binding domains switched, and between KIF5 loaded with VAMP2 versus GluR2 suggest that axonal entry of vesicular carriers depends on the transport efficacy of KIF-cargo complexes. This selective AIS filtering may contribute to preferential trafficking and segregation of cellular components in polarized neurons.