How molecular motors are arranged on a cargo is important for vesicular transport.
How molecular motors are arranged on a cargo is important for vesicular transport.
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DOI：
10.1371/journal.pcbi.1002032
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发表时间：
2011-05
影响因子：
4.3
通讯作者：
Yu CC
中科院分区：
文献类型：
--
作者：
Erickson RP;Jia Z;Gross SP;Yu CC
细胞的空间组织依赖于分子马达蛋白驱动蛋白、动力蛋白和肌球蛋白沿沿着微管和肌动蛋白丝运送的货物的细胞内运输。虽然我们对单个马达的功能了解很多，但有重要证据表明，体内的货物是由多个马达携带的。虽然多运动功能的某些方面已经受到关注，但货物本身-以及货物上的运动组织-如何影响运输尚未被考虑。为了解决这个问题，我们已经开发了一个三维的Monte Carlo模拟电机运输的球形货物，受到热波动，产生旋转和平移扩散。我们发现，这些波动会对马达施加负载，显著降低大型货物的平均行程距离和速度，特别是在大粘度下。此外，货物的存在可以极大地帮助马达有效地结合到微管上：中等大小的货物相对缓慢的平移和旋转扩散使马达有足够的机会在马达/货物集合扩散出微管的范围之前结合到微管上。对于快速扩散的货物，如果附近有微管，它们可以很容易地通过平移扩散到达，它们与微管结合的概率很高。我们的模拟发现，电机可能长约100 nm的一个原因是，当连接到大尺寸的货物时，可以提高它们的“开启”率。最后，我们的研究结果表明，为了有效地调节活跃电机的数量，电机应该聚集在一起，而不是随机分布在货物表面。虽然我们的模拟使用了驱动蛋白的特定参数，但这些效果是由马达、货物和细丝的一般属性引起的，因此它们也应该适用于其他马达。活细胞的空间组织依赖于由分子马达蛋白组成的运输系统，分子马达蛋白的作用就像搬运工沿着类似于道路的细丝运送货物。这种运输系统的崩溃与神经退行性疾病有关，如阿尔茨海默病和亨廷顿病。在活细胞中，货物通常由多个马达携带。虽然多运动功能的某些方面受到了关注，但货物本身如何影响运输尚未得到考虑。为了解决这个问题，我们开发了一个三维的计算机模拟电机运输的球形货物时产生的波动，在细胞内环境中的小分子冲击货物。这些波动会导致货物拉动马达，使马达减速并使它们脱离灯丝（道路）。这种影响随着货物尺寸和介质粘度的增加而增加。我们还发现，货物的存在有助于马达在漂流之前与细丝结合。如果存在其他细丝，那么货物可以结合到其中一个。我们的研究结果还表明，它是更好地组的电机上的货物，而不是分散他们随机在表面上。
The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself —and motor organization on the cargo—affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their ‘on’ rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well. The spatial organization of living cells depends upon a transportation system consisting of molecular motor proteins that act like porters carrying cargos along filaments that are analogous to roads. The breakdown of this transportation system has been associated with neurodegenerative diseases such as Alzheimer's and Huntington's disease. In living cells, cargos are typically carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself affects transport has not been considered. To address this, we developed a three-dimensional computer simulation of motors transporting a spherical cargo subject to fluctuations produced when small molecules in the intracellular environment buffet the cargo. These fluctuations can cause the cargo to pull on the motors, slowing them down and making them detach from the filament (road). This effect increases as the cargo size and viscosity of the medium increase. We also found that the presence of the cargo helped the motors to bind to a filament before it drifted away. If other filaments were present, then the cargo could bind to one of them. Our results also indicated that it is better to group the motors on the cargo rather than spread them randomly over the surface.
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影响因子：
2.4
作者：
Muhuri, Sudipto;Pagonabarraga, Ignacio
通讯作者：
Pagonabarraga, Ignacio
影响因子：
7.5
作者：
Gennerich A;Vale RD
通讯作者：
Vale RD
DOI：
10.1007/bf01181656
发表时间：
1976-01-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
COOK, RD;BURNSTOCK, G
通讯作者：
BURNSTOCK, G
影响因子：
21.3
作者：
King, SJ;Schroer, TA
通讯作者：
Schroer, TA
DOI：
10.1007/bf01953125
发表时间：
1976-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
ERANKO, O;KLINGE, E;SJOSTRAND, NO
通讯作者：
SJOSTRAND, NO