Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
J Neurosci. 2011 Feb 9;31(6):2216-24. doi: 10.1523/JNEUROSCI.2653-10.2011.
Kinesin-1 is a microtubule plus-end-directed motor that transports various cargos along the axon. Previous studies have elucidated the physical and genetic interactions between kinesin-1 and cytoplasmic dynein, a microtubule minus-end-directed motor, in neuronal cells. However, the physiological importance of kinesin-1 in the dynein-dependent retrograde transport of cargo molecules remains obscure. Here, we show that Caenorhabditis elegans kinesin-1 forms a complex with dynein via its interaction with UNC-16, which binds to the dynein light intermediate (DLI) chain. Both kinesin-1 and UNC-16 are required for localization of DLI-1 at the plus ends of nerve process microtubules. In addition, retrograde transport of APL-1 depends on kinesin-1, UNC-16, and dynein. These results suggest that kinesin-1 mediates the anterograde transport of dynein using UNC-16 as a scaffold and that dynein in turn mediates the retrograde transport of cargo molecules in vivo. Thus, UNC-16 functions as an adaptor for kinesin-1-mediated transport of dynein.
驱动蛋白-1 是一种微管正极导向马达，它能沿轴突运输各种货物。以前的研究已经阐明了神经元细胞中驱动蛋白-1 和细胞质动力蛋白之间的物理和遗传相互作用，细胞质动力蛋白是一种微管负极导向马达。然而，驱动蛋白-1 在货物分子依赖动力蛋白的逆行运输中的生理重要性仍然不清楚。在这里，我们表明秀丽隐杆线虫的驱动蛋白-1 通过与 UNC-16 的相互作用与动力蛋白形成复合物，UNC-16 结合动力蛋白轻中间链（DLI）。DLI-1 在神经过程微管正极的定位需要驱动蛋白-1 和 UNC-16。此外，APL-1 的逆行运输依赖于驱动蛋白-1、UNC-16 和动力蛋白。这些结果表明，驱动蛋白-1 利用 UNC-16 作为支架介导动力蛋白的正向运输，而动力蛋白反过来在体内介导货物分子的逆行运输。因此，UNC-16 作为驱动蛋白-1 介导的动力蛋白运输的衔接子发挥作用。
