Department of Chemistry, Rice University, Houston, Texas 77005, USA.
J Biol Chem. 2012 Jan 27;287(5):3357-65. doi: 10.1074/jbc.M111.296582. Epub 2011 Dec 9.
Microtubule-dependent transport is most often driven by collections of kinesins and dyneins that function in either a concerted fashion or antagonistically. Several lines of evidence suggest that cargo transport may not be influenced appreciably by the combined action of multiple kinesins. Yet, as in previous optical trapping experiments, the forces imposed on cargos will vary spatially and temporally in cells depending on a number of local environmental factors, and the influence of these conditions has been largely overlooked. Here, we characterize the dynamics of structurally defined complexes containing multiple kinesins under the controlled loads of an optical force clamp. While demonstrating that there are generic kinetic barriers that restrict the ability of multiple kinesins to cooperate productively, the spatial and temporal properties of applied loads is found to play an important role in the collective dynamics of multiple motor systems. We propose this dependence has implications for intracellular transport processes, especially for bidirectional transport.
微管依赖的运输通常是由协同或拮抗作用的驱动蛋白和动力蛋白集合驱动的。有几条证据表明,货物运输可能不会受到多个驱动蛋白协同作用的显著影响。然而,与之前的光学捕获实验一样,由于细胞内存在许多局部环境因素,作用在货物上的力会在空间和时间上发生变化,而这些条件的影响在很大程度上被忽视了。在这里,我们在光力钳的受控负载下对含有多个驱动蛋白的结构定义复合物的动力学进行了表征。虽然证明了存在通用的动力学障碍,限制了多个驱动蛋白进行有效合作的能力,但施加负载的空间和时间特性在多个马达系统的集体动力学中起着重要作用。我们提出这种依赖性对细胞内运输过程有影响,特别是对双向运输有影响。