Mixed Microtubules Steer Dynein-Driven Cargo Transport into Dendrites
Mixed Microtubules Steer Dynein-Driven Cargo Transport into Dendrites
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DOI：
10.1016/j.cub.2009.12.052
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发表时间：
2010-02-23
期刊：
影响因子：
9.2
通讯作者：
Hoogenraad, Casper C.
中科院分区：
文献类型：
--
作者：
Kapitein, Lukas C.;Schlager, Max A.;Hoogenraad, Casper C.
背景资料：为了建立和维持它们的极化形态，神经元采用由分子马达驱动的主动运输来在轴突和树突之间分类货物。然而，神经元微管arrays. Results的极化运输的基本交通规则尚不清楚：在这里，我们表明，微管负端定向运动动力蛋白是所需的树突特异性货物，如AMPA受体的极化靶向。为了直接研究动力蛋白马达如何促进极化树突转运，我们在海马神经元中建立了一种选择性探测特定马达蛋白活性的贩运测定。这表明，与驱动蛋白不同，动力蛋白马达选择性地驱动货物进入树突，由它们的混合微管阵列控制。此外，轴突特异性货物，如突触前囊泡蛋白突触素，通过耦合动力蛋白马达重定向到树突。定量建模表明，双向动力蛋白驱动的混合微管运输提供了一个有效的机制，建立一个稳定的密度不断更新的小泡在dendrites.Conclusions：这些结果表明，一个强大的方法来研究特定的运动蛋白活性活细胞内，并意味着在树突状细胞运输动力蛋白的关键作用。我们建议，动力蛋白建立树突状货物的初始排序和额外的马达蛋白协助随后的交付。
Background: To establish and maintain their polarized morphology, neurons employ active transport driven by molecular motors to sort cargo between axons and dendrites. However, the basic traffic rules governing polarized transport on neuronal microtubule arrays are unclear.Results: Here we show that the microtubule minus-end-directed motor dynein is required for the polarized targeting of dendrite-specific cargo, such as AMPA receptors. To directly examine how dynein motors contribute to polarized dendritic transport, we established a trafficking assay in hippocampal neurons to selectively probe specific motor protein activity. This revealed that, unlike kinesins, dynein motors drive cargo selectively into dendrites, governed by their mixed microtubule array. Moreover, axon-specific cargos, such as presynaptic vesicle protein synaptophysin, are redirected to dendrites by coupling to dynein motors. Quantitative modeling demonstrated that bidirectional dynein-driven transport on mixed microtubules provides an efficient mechanism to establish a stable density of continuously renewing vesicles in dendrites.Conclusions: These results demonstrate a powerful approach to study specific motor protein activity inside living cells and imply a key role for dynein in dendritic transport. We propose that dynein establishes the initial sorting of dendritic cargo and additional motor proteins assist in subsequent delivery.