Department of Neuroscience, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Curr Biol. 2010 Feb 23;20(4):290-9. doi: 10.1016/j.cub.2009.12.052. Epub 2010 Feb 4.
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.
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.
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.
为了建立和维持其极化形态，神经元利用分子马达驱动的主动运输在轴突和树突之间分拣货物。然而，指导神经元微管列阵中极化运输的基本交通规则尚不清楚。
在这里，我们表明微管负向导向的马达动力蛋白对于树突特异性货物（如 AMPA 受体）的极化靶向是必需的。为了直接研究动力蛋白马达如何有助于极化树突运输，我们在海马神经元中建立了一个运输测定法，以选择性地探测特定的运动蛋白活性。这表明，与驱动蛋白不同，动力蛋白马达通过其混合微管列阵将货物选择性地输送到树突中。此外，轴突特异性货物，如突触小体蛋白 synaptophysin，通过与动力蛋白马达偶联被重新引导到树突中。定量建模表明，混合微管上的双向动力蛋白驱动运输为在树突中建立稳定的不断更新的囊泡密度提供了一种有效的机制。
这些结果表明了一种在活细胞内研究特定运动蛋白活性的有力方法，并暗示了动力蛋白在树突运输中的关键作用。我们提出动力蛋白建立了树突货物的初始分拣，并且其他的运动蛋白在随后的递送上提供帮助。
