轴突起始段胞浆屏障与神经元蛋白的极性分布

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。我们的研究发现．培养的海马神经元在轴突／树突分化后的两天内，轴突起始段出现一个由微丝纤维和AnkyrinG构成的分子筛，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，是膜蛋白能否通过该分子筛的决定条件。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，不能穿越这个屏障。轴突起始段胞浆屏障这种选择性的滤过功能对维持神经元蛋白的极性转运和分布十分重要。

A Selective Filter for Cytoplasmic Transport at the Axon Initial Segment

Distinct cellular components are segregated into the somatodendritic and axonal compartments of polarized neurons, but mechanisms underlying the development and maintenance of such segregation remain largely clear. In cultured hippocampal neurons, we observed an ankyrinG- and F-actin-dependent structure that e- merged in the cytoplasm of the axon initial segment （AIS） within two days after axon/dendrite differentiation, imposing a selective filter for the diffusion of macromolecules and the 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 vs. GluR2 suggest that axonal entry of vesicular carriers through AIS depends on the transport efficacy of the KIF-cargo complexes. This selective AIS filtering may contribute to preferential trafficking and segregation of cellular components in polarized neurons.