Adaptive braking by Ase1 prevents overlapping microtubules from sliding completely apart
Adaptive braking by Ase1 prevents overlapping microtubules from sliding completely apart
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DOI：
10.1038/ncb2323
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发表时间：
2011-10-01
影响因子：
21.3
通讯作者：
Janson, Marcel E.
中科院分区：
文献类型：
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作者：
Braun, Marcus;Lansky, Zdenek;Janson, Marcel E.
反平行微管末端之间的短重叠区域是双极微管阵列中的中心元素。虽然它们的形成需要马达（1），但最近的体外研究表明，单靠分子马达无法产生稳定的重叠。马达可以使微管沿着彼此滑动直到完全分离（2-4），或者在存在相对马达的情况下产生振荡运动（5-7）。在这里，我们表明，Ase 1，保守的MAP 65/PRC 1家族的微管捆绑蛋白的成员，使形成稳定的反平行重叠，通过自适应制动驱动蛋白-14驱动的微管-微管滑动。当重叠的微管开始滑动分开时，Ase 1分子在收缩的重叠中变得紧凑，滑动速度以剂量依赖性方式逐渐降低。压实是由移动微管末端作为Ase 1扩散的障碍。定量建模表明，Ase 1的分子解离速率足够低，能够在数十分钟内保持重叠稳定。自适应制动的发现表明，滑动可以在局部减慢，以稳定双极阵列中心的重叠，而滑动在其他地方进行，使网络自组织。
Short regions of overlap between ends of antiparallel microtubules are central elements within bipolar microtubule arrays. Although their formation requires motors(1), recent in vitro studies demonstrated that stable overlaps cannot be generated by molecular motors alone. Motors either slide microtubules along each other until complete separation(2-4) or, in the presence of opposing motors, generate oscillatory movements(5-7). Here, we show that Ase1, a member of the conserved MAP65/PRC1 family of microtubule-bundling proteins, enables the formation of stable antiparallel overlaps through adaptive braking of Kinesin-14-driven microtubule-microtubule sliding. As overlapping microtubules start to slide apart, Ase1 molecules become compacted in the shrinking overlap and the sliding velocity gradually decreases in a dose-dependent manner. Compaction is driven by moving microtubule ends that act as barriers to Ase1 diffusion. Quantitative modelling showed that the molecular off-rate of Ase1 is sufficiently low to enable persistent overlap stabilization over tens of minutes. The finding of adaptive braking demonstrates that sliding can be slowed down locally to stabilize overlaps at the centre of bipolar arrays, whereas sliding proceeds elsewhere to enable network self-organization.