Axonal transport cargo motor count versus average transport velocity: Is fast versus slow transport really single versus multiple motor transport?
Axonal transport cargo motor count versus average transport velocity: Is fast versus slow transport really single versus multiple motor transport?
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DOI：
10.1016/j.jtbi.2015.01.010
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发表时间：
2015-04-07
影响因子：
2
通讯作者：
Mitchell, Cassie S.
中科院分区：
文献类型：
--
作者：
Lee, Robert H.;Mitchell, Cassie S.
观察到货物表现出“走走停停”的行为(即货物“停顿”)，通常认为这种数秒的停顿可以归因于在汽车行进过程中向货物行驶的马达同样长的停顿。我们认为，仔细检查分离的微管实验记录并不支持运动暂停。相反，我们认为，数据表明，汽车货物复合体遇到了阻碍前进、最终分离和重新连接的障碍，这种受阻-分离-重新连接的序列在轴突中被观察到是一种“暂停”。在此基础上，结合我们基于定量证据的观点，即慢速轴突运输实际上是单马达和多马达运输，我们开发了一个货位马达模型，仅通过改变所涉及的马达数量就能够展示从慢到快运输的全部范围。这个由一级动力学推导的计算模型既适用于动蛋白，也适用于动力蛋白，并考虑了负荷依赖性以及马达在前进过程中遇到障碍的情况。该模型做出了以下具体预测：从结合到阻塞的平均距离约为10微米；轴突的平均运动最大速度至少为6微米/S；最快的运输需要至少10个马达，而慢速运输只需要一个马达；单个体内货物连接的马达可能只花5%的时间沿着微管处理，其余的时间要么被阻塞要么被解绑在微管上；至少在神经丝运输的情况下，动蛋白和动力蛋白基本上不是在进行“拔河”竞争。(C)2015年提交人。爱思唯尔有限公司出版。
Cargos have been observed exhibiting a "stop-and-go" behavior (i.e. cargo "pause"), and it has generally been assumed that these multi-second pauses can be attributed to equally long pauses of cargo-bound motors during motor procession. We contend that a careful examination of the isolated microtubule experimental record does not support motor pauses. Rather, we believe that the data suggests that motor cargo complexes encounter an obstruction that prevents procession, eventually detach and reattach, with this obstructed-detach-reattach sequence being observed in axon as a "pause." Based on this, along with our quantitative evidence-based contention that slow and fast axonal transport are actually single and multi-motor transport, we have developed a cargo level motor model capable of exhibiting the full range of slow to fast transport solely by changing the number of motors involved. This computational model derived using first-order kinetics is suitable for both kinesin and dynein and includes load-dependence as well as provision for motors encountering obstacles to procession. The model makes the following specific predictions: average distance from binding to obstruction is about 10 mu m; average motor maximum velocity is at least 6 mu m/s in axon; a minimum of 10 motors is required for the fastest fast transport while only one motor is required for slow transport; individual in-vivo cargo-attached motors may spend as little as 5% of their time processing along a microtubule with the remainder being spent either obstructed or unbound to a microtubule; and at least in the case of neurofilament transport, kinesin and dynein are largely not being in a "tug-of-war" competition. (C) 2015 The Authors. Published by Elsevier Ltd.