Microtubules originate asymmetrically at the somatic Golgi and are guided via Kinesin2 to maintain polarity within neurons

Microtubules originate asymmetrically at the somatic Golgi and are guided via Kinesin2 to maintain polarity within neurons
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微管不对称地起源于体细胞高尔基体,并通过驱动蛋白 2 引导以维持神经元内的极性

DOI:
10.1101/846832
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发表时间:
2019
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通讯作者:
Mukherjee A
Mukherjee A
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作者:
Mukherjee A

文献摘要

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神经元包含对神经元功能至关重要的极化微管阵列。微管的正端快速增长,负端稳定;轴突内的正端向外生长(正端向外),而树突内的正端向外生长(负端向外)。微管是如何成核的,以及微管极性是如何在神经元内建立和维持的,目前还不清楚。我们发现在果蝇动脉瘤中,主要的微管成核复合物γ- turc定位于体细胞高尔基体,高尔基体优先向轴突成核微管。我们发现运动蛋白-2,一种正端相关的马达,沿着相邻的微管“行走”,引导这些生长的微管进入轴突。相反,驱动蛋白-2阻止生长的微管进入树突。我们提出,当正端相关的驱动蛋白-2与极性相反的树突微管接触时,这种排斥就会发生,在生长的正端产生向后的失速力。因此,不对称成核和kinesin -2介导的微管引导有助于轴突内的正端向外极性和维持树突内的负端向外极性。
Neurons contain polarised microtubule arrays essential for neuronal function. Microtubules have fast-growing plus ends and stable minus ends; within axons plus ends grow away from the soma (plus-end-out) and within dendrites they grow towards the soma (minus-end-out). How microtubules are nucleated and how microtubule polarity is established and maintained within neurons remains unclear. We show that withinDrosophilaneurons the major microtubule nucleating complexes, γ-TuRCs, localise to the somatic Golgi, which nucleates microtubules preferentially towards the axon. We find that Kinesin-2, a plus-end-associated motor that “walks’’ along adjacent microtubules, guides these growing microtubules into axons. In contrast, Kinesin-2 prevents growing microtubules from entering dendrites. We propose that this exclusion occurs when plus-end-associated Kinesin-2 engages with dendritic microtubules of opposite polarity, generating a backward stalling force on the growing plus end. Thus, asymmetric nucleation and Kinesin-2-mediated microtubule guidance contribute to plus-end-out polarity within axons and maintain minus-end-out polarity in dendrites.