Department of Developmental and Cell Biology, University of California, Irvine, CA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Traffic. 2017 Oct;18(10):658-671. doi: 10.1111/tra.12504. Epub 2017 Sep 8.
The kinesin family proteins are often studied as prototypical molecular motors; a deeper understanding of them can illuminate regulation of intracellular transport. It is typically assumed that they function identically. Here we find that this assumption of homogeneous function appears incorrect: variation among motors' velocities in vivo and in vitro is larger than the stochastic variation expected for an ensemble of "identical" motors. When moving on microtubules, slow and fast motors are persistently slow, and fast, respectively. We develop theory that provides quantitative criteria to determine whether the observed single-molecule variation is too large to be generated from an ensemble of identical molecules. To analyze such heterogeneity, we group traces into homogeneous sub-ensembles. Motility studies varying the temperature, pH and glycerol concentration suggest at least 2 distinct functional states that are independently affected by external conditions. We end by investigating the functional ramifications of such heterogeneity through Monte-Carlo multi-motor simulations.
驱动蛋白家族蛋白常被作为典型的分子马达进行研究；深入了解它们可以阐明细胞内运输的调控机制。通常假设它们的功能是相同的。然而，我们发现这种同功假设是不正确的：在体内和体外，马达速度的变化比预期的一组“相同”马达的随机变化更大。当在微管上运动时，慢和快的马达分别持续缓慢和快速运动。我们提出了一种理论，提供了定量的标准来确定观察到的单个分子的变化是否太大，以至于不能从一组相同的分子中产生。为了分析这种异质性，我们将轨迹分为同质的子集合。改变温度、pH 值和甘油浓度的运动性研究表明，至少有 2 种不同的功能状态，它们分别受到外部条件的影响。最后，我们通过蒙特卡罗多马达模拟研究了这种异质性的功能后果。
