Kinesin-2 from C. reinhardtii Is an Atypically Fast and Auto-inhibited Motor that Is Activated by Heterotrimerization for Intraflagellar Transport.
Kinesin-2 from C. reinhardtii Is an Atypically Fast and Auto-inhibited Motor that Is Activated by Heterotrimerization for Intraflagellar Transport.
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DOI：
10.1016/j.cub.2020.01.046
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发表时间：
2020-03-23
期刊：
影响因子：
--
通讯作者：
Ökten Z
中科院分区：
文献类型：
--
作者：
Sonar P;Youyen W;Cleetus A;Wisanpitayakorn P;Mousavi SI;Stepp WL;Hancock WO;Tüzel E;Ökten Z
几乎所有纤毛的构建和功能都需要普遍保守的鞭毛内转运（IFT）过程。在绿色C-C中的快速界面张力期间。Reinhardtii，平均10个驱动蛋白-2马达在火车上以紧密的装配“排列”，引发了这些马达如何协调它们的动作以确保沿着鞭毛沿着平稳和快速的运输而不妨碍彼此的问题。在这里，我们表明，异源二聚体FLA 8/10驱动蛋白-2单独负责在C.莱因哈德氏菌值得注意的是，在单分子研究中，FLA 8/10以与体内IFT相匹配的速度移动，但另外显示出缓慢的速度分布，表明了自抑制。添加KAP亚基以产生异源三聚体的FLA 8/10/KAP缓解了这种抑制，从而为KAP亚基在体内完全激活FLA 8/10用于IFT中的异源三聚体化提供了机制原理。最后，我们从C. reinhardtii和C. elegans通过DNA系链来了解体内IFT期间运动协调的分子基础。对于来自两个物种的马达对，共运输速度非常接近于单分子速度，并且两个复合物花费大约80%的时间，其中两个马达中只有一个附着在微管上。因此，无论基因和动力学性质如何，驱动蛋白-2马达大多单独工作而不牺牲效率。因此，我们的研究结果提供了一个简单的机制，尽管是由具有不同特性的电机进行的，但在不同的生物体中如何实现有效的IFT。Sonar等解释了单细胞绿色藻类C. reinhardtii和提供了一个简单的模型的运动合作在远亲单细胞和多细胞生物体，这是非常相似的。
Construction and function of virtually all cilia require the universally conserved process of Intraflagellar Transport (IFT). During the atypically fast IFT in the green alga C. reinhardtii, on average ten kinesin-2 motors ‘line up’ in a tight assembly on the trains, provoking the question of how these motors coordinate their action to ensure smooth and fast transport along the flagellum without standing in each other’s way. Here, we show that the heterodimeric FLA8/10 kinesin-2 alone is responsible for the atypically fast IFT in C. reinhardtii. Notably, in single-molecule studies, FLA8/10 moved at speeds matching those of in vivo IFT, but additionally displayed a slow velocity distribution, indicative of auto-inhibition. Addition of the KAP subunit to generate the heterotrimeric FLA8/10/KAP relieved this inhibition, thus providing a mechanistic rationale for heterotrimerization with the KAP subunit in fully activating FLA8/10 for IFT in vivo. Finally, we linked fast FLA8/10 and slow KLP11/20 kinesin-2 from C. reinhardtii and C. elegans through a DNA-tether to understand the molecular underpinnings of motor coordination during IFT in vivo. For motor pairs from both species, the co-transport velocities very nearly matched the single-molecule velocities, and both complexes spent roughly 80% of the time with only one of the two motors attached to the microtubule. Thus, irrespective of phylogeny and kinetic properties, kinesin-2 motors work mostly alone without sacrificing efficiency. Our findings thus offer a simple mechanism for how efficient IFT is achieved across diverse organisms despite being carried out by motors with different properties. Sonar et al. explain the mechanism of the atypically fast kinesin-2-driven Intraflagellar Transport in the uni-cellular green algae C. reinhardtii and provide a simple model of motor cooperation in distantly related uni- and multi-cellular organisms, which turns out to be remarkably similar.
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DOI：
10.1126/science.1204824
发表时间：
2011-08-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
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影响因子：
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发表时间：
2009-03-03
影响因子：
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通讯作者：
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DOI：
10.1083/jcb.201001057
发表时间：
2010-06-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hammond JW;Blasius TL;Soppina V;Cai D;Verhey KJ
通讯作者：
Verhey KJ
DOI：
10.1083/jcb.141.4.993
发表时间：
1998-05-18
期刊：
The Journal of cell biology
影响因子：
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