Li Jun, Lee Wei-Lih, Cooper John A
Department of Cell Biology and Physiology, Washington University in St Louis, School of Medicine, St Louis, MO 63110, USA.
Nat Cell Biol. 2005 Jul;7(7):686-90. doi: 10.1038/ncb1273. Epub 2005 Jun 19.
Dynein is a minus-end-directed microtubule motor with critical roles in mitosis, membrane transport and intracellular transport. Several proteins regulate dynein activity, including dynactin, LIS1 (refs 2, 3) and NudEL (NudE-like). Here, we identify a NUDEL homologue in budding yeast and name it Ndl1. The ndl1delta null mutant shows decreased targeting of dynein to microtubule plus ends, an essential element of the model for dynein function. We find that Ndl1 regulates dynein targeting through LIS1, with which it interacts biochemically, but not through CLIP170, another plus-end protein involved in dynein targeting. Ndl1 is found at far fewer microtubule ends than are LIS1 and dynein. However, when Ndl1 is present at a plus end, the molar amount of Ndl1 approaches that of LIS1 and dynein. We propose a model in which Ndl1 binds transiently to the plus end to promote targeting of LIS1, which cooperatively recruits dynein.
动力蛋白是一种向微管负端移动的分子马达，在有丝分裂、膜运输和细胞内运输中发挥关键作用。有几种蛋白质可调节动力蛋白的活性，包括动力肌动蛋白、LIS1（参考文献2、3）和NudEL（类NudE）。在此，我们在芽殖酵母中鉴定出一种NUDEL同源物，并将其命名为Ndl1。ndl1δ缺失突变体显示动力蛋白向微管正端的靶向作用减弱，这是动力蛋白功能模型的一个关键要素。我们发现Ndl1通过LIS1调节动力蛋白的靶向作用，二者存在生化相互作用，但不是通过CLIP170（另一种参与动力蛋白靶向作用的正端蛋白）。与LIS1和动力蛋白相比，在微管末端发现的Ndl1要少得多。然而，当Ndl1存在于正端时，其摩尔量接近LIS1和动力蛋白。我们提出了一个模型，即Ndl1与正端短暂结合以促进LIS1的靶向作用，LIS1协同招募动力蛋白。
