MAP7 regulates organelle transport by recruiting kinesin-1 to microtubules
MAP7 regulates organelle transport by recruiting kinesin-1 to microtubules
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DOI：
10.1074/jbc.ra119.008052
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发表时间：
2019-06-28
影响因子：
4.8
通讯作者：
Hendricks, Adam G.
中科院分区：
文献类型：
--
作者：
Chaudhary, Abdullah R.;Lu, Hailong;Hendricks, Adam G.
微管相关蛋白（MAPs）调节微管聚合、动力学和组织。此外，map改变动力蛋白和动力蛋白的运动性，以控制沿微管的运输。MAP7 （ensconsin, E-MAP-115）是一种普遍存在的MAP，在有丝分裂和神经元分支中组织微管细胞骨架。MAP7也向微管招募运动蛋白-1。为了了解MAP7激活kinesin-1如何调节由kinesin和dynein组合运输的细胞器的运动，我们分离了细胞器并在体外重建了它们的运动。在缺乏MAP7的情况下，分离的吞噬体沿微管表现出大约相等的正端和负端定向运动。MAP7引起运动性的显著变化；吞噬体在80%的时间里向正端移动，而驱动蛋白团队产生更多的力量。为了剖析map7介导的激酶-1驱动运输的调节，我们研究了它对单个和全长激酶-1马达组的运动性和力产生的影响。我们发现MAP7不会改变单个kineins -1马达施加的力，而是增加其与微管的结合率。对于驱动蛋白的集合，更多的驱动蛋白马达同时参与并产生力，优先将细胞器靶向微管正端。
Microtubule-associated proteins (MAPs) regulate microtubule polymerization, dynamics, and organization. In addition, MAPs alter the motility of kinesin and dynein to control trafficking along microtubules. MAP7 (ensconsin, E-MAP-115) is a ubiquitous MAP that organizes the microtubule cytoskeleton in mitosis and neuronal branching. MAP7 also recruits kinesin-1 to microtubules. To understand how the activation of kinesin-1 by MAP7 regulates the motility of organelles transported by ensembles of kinesin and dynein, we isolated organelles and reconstituted their motility in vitro. In the absence of MAP7, isolated phagosomes exhibit approximately equal fractions of plus- and minus-end-directed motility along microtubules. MAP7 causes a pronounced shift in motility; phagosomes move toward the plus-end similar to 80% of the time, and kinesin teams generate more force. To dissect MAP7-mediated regulation of kinesin-driven transport, we examined its effects on the motility and force generation of single and teams of full-length kinesin-1 motors. We find that MAP7 does not alter the force exerted by a single kinesin-1 motor, but instead increases its binding rate to the microtubule. For ensembles of kinesin, a greater number of kinesin motors are simultaneously engaged and generating force to preferentially target organelles toward the microtubule plus-end.