中科院神經(jīng)所蒲慕明和段樹民帶領的研究團隊在新一期Cell發(fā)表了有關神經(jīng)元蛋白極性分布機制的最新研究論文,。
神經(jīng)元是一種極性細胞,，以軸突的起始段為界，可分為軸突和胞體樹突兩大部分,。樹突負責接收信息,，軸突則負責輸出信息。這種不對稱的功能,，依賴于不同功能的蛋白在軸突和樹突上的不對稱分布,。神經(jīng)元蛋白的極性分布如何形成以及維持，是神經(jīng)生物學領域的重要問題,。
來自神經(jīng)所的報道稱,，研究小組發(fā)現(xiàn)在接近胞體的軸突起始段（AIS）存在一個由肌動蛋白和Ankyrin G構(gòu)成的分子篩,，像濾網(wǎng)一樣限制了大分子蛋白在軸突和胞體之間的擴散，但允許某些依賴特定馬達蛋白轉(zhuǎn)運的膜蛋白通過,。
進一步的研究發(fā)現(xiàn),，馬達蛋白驅(qū)動力的強弱，以及膜蛋白-馬達蛋白復合體運輸效能的高低,，是膜蛋白能否通過AIS分子篩的決定條件,。軸突膜蛋白轉(zhuǎn)運復合體VAMP2-KIF5的運輸效能較高，可以穿過分子篩從胞體轉(zhuǎn)運到軸突內(nèi),，而樹突膜蛋白轉(zhuǎn)運復合體NR2B-KIF17和GluR2-KIF5的運輸效能較低,，不能穿越這個胞漿屏障。這一新穎的機制,，為研究神經(jīng)元蛋白的極性分布提供了嶄新的角度,，具有重要的理論意義。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
