蒲慕明最新《Cell》文章

09年3月6日新鲜出炉的网络版《Cell》提前发表了来自中国神经科学研究所蒲慕明的最新研究性文章，文章以A Selective Filter for Cytoplasmic Transport at the Axon Initial Segment 为题，主要解析了神经元蛋白极性分布机制的研究成果。

　　

生物通综合，中科院神经科学研究所近两年来频频出成果，09年3月6日新鲜出炉的网络版《Cell》提前发表了来自中国神经科学研究所蒲慕明的最新研究性文章，据悉该研究性文章将在下一期的印刷版《Cell》正式发表。

蒲慕明目前任神经科学研究所所长，自上任以来带领神经科学研究所取得了令人瞩目的研究成果。蒲慕明是神经可塑性研究组的组长，目前进行的研究课题主要有：神经环路的可塑性，从神经可塑性到大脑的发育。

文章以A Selective Filter for Cytoplasmic Transport at the Axon Initial Segment 为题，主要解析了神经元蛋白极性分布机制的研究成果。

文章第一作者是蒲慕明和段树民两位研究员联合指导的博士生宋瑷宏，通讯作者是蒲慕明研究员和段树民研究员。

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。

（生物通 小茜）

生物通推荐原文摘要：A Selective Filter for Cytoplasmic Transport at the Axon Initial Segment 

【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.

蒲慕明代表性作品：

Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones. [G.X. Wang, and M-m. Poo (2005) Nature 434, 898-904]

Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system. [J. Du, and M-m. Poo (2004) Nature 429, 878-83]

Reversal and stabilization of synaptic modifications in a developing visual system. [Q. Zhou, H. Tao, and M-m. Poo (2003) Science  300, 1953-57]

Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons. [F. Engert, H.W. Tao, L.I. Zhang, and M-m. Poo (2002) Nature 419, 470-475]

Adaptation in the chemotactic guidance of nerve growth cones. [G. Ming, S.F. Wong, J. Henley, X. Yuan, H. Song, N.C. Spitzer, and M-m. Poo (2002) Nature 417, 411-418]

Neurotrophins as synaptic modulators. [M-m. Poo (2001) Nature Reviews Neurosci. 2, 24-32]

Synaptic modification by correlated activity: Hebb's postulate revisited. [G. Bi, and M-m. Poo (2001) Annu. Rev. Neurosci. 24, 139-166]

GABA itself promotes the developmental switch of neuronal GABAergic transmission from excitation to inhibition. [K. Ganguly, A. Schinder, and M-m. Poo (2001) Cell 105, 521-532]

Calcium signaling in the guidance of nerve growth by netrin-1. [K. Hong, M. Nishiyama, J. Henley, M. Tessier-Lavigne, and M-m. Poo (2000) Nature 403, 93-98]

Distributed synaptic modification in neural networks induced by patterned stimulation. [G. Bi and M-m. Poo (1999) Nature 401, 792-796]

Gating of BDNF-induced synaptic potentiation by cAMP. [L Boulanger, and M-m. Poo (1999) Science 284, 1982-1984]

A critical window in the cooperation and competition among developing retinotectal synapses. [L. Zhang, H-z. Tao, C. Holt, W. Harris, and M-m Poo (1998) Nature 395, 37-44]

Propagation of activity-dependent synaptic depression in small neural networks. [R. Fitzsimonds, H-j. Song, and M-m Poo (1997) Nature 388, 439-448]

A cAMP-induced switching of turning direction of nerve growth cones. [H. Song, G. Ming, and M-m. Poo (1997) Nature 388, 275-279]