Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Cell Biol. 2012 Aug 20;198(4):491-9. doi: 10.1083/jcb.201205090.
Polo-like kinase-1 (Plk1) is a highly conserved kinase with multiple mitotic functions. Plk1 localizes to prometaphase kinetochores and is reduced at metaphase kinetochores, similar to many checkpoint signaling proteins, but Plk1 is not required for spindle checkpoint function. Plk1 is also implicated in stabilizing kinetochore-microtubule attachments, but these attachments are most stable when kinetochore Plk1 levels are low at metaphase. Therefore, it is unclear how Plk1 function at kinetochores can be understood in the context of its dynamic localization. In this paper, we show that Plk1 activity suppresses kinetochore-microtubule dynamics to stabilize initial attachments in prometaphase, and Plk1 removal from kinetochores is necessary to maintain dynamic microtubules in metaphase. Constitutively targeting Plk1 to kinetochores maintained high activity at metaphase, leading to reduced interkinetochore tension and intrakinetochore stretch, a checkpoint-dependent mitotic arrest, and accumulation of microtubule attachment errors. Together, our data show that Plk1 dynamics at kinetochores control two critical mitotic processes: initially establishing correct kinetochore-microtubule attachments and subsequently silencing the spindle checkpoint.
丝氨酸/苏氨酸激酶 Polo 样激酶-1（Plk1）是一种高度保守的激酶，具有多种有丝分裂功能。Plk1 定位于前期的动粒上，在中期的动粒上减少，类似于许多检查点信号蛋白，但 Plk1 不是纺锤体检查点功能所必需的。Plk1 还涉及稳定动粒-微管连接，但当中期动粒 Plk1 水平较低时，这些连接最稳定。因此，尚不清楚 Plk1 在动粒上的功能如何在其动态定位的背景下得到理解。在本文中，我们表明 Plk1 活性抑制动粒-微管动力学，以稳定前期的初始连接，并且 Plk1 从动粒上的去除对于维持中期的动态微管是必需的。组成性地将 Plk1 靶向动粒保持中期的高活性，导致动粒间张力和动粒内拉伸减少、检查点依赖的有丝分裂停滞以及微管连接错误的积累。总之，我们的数据表明 Plk1 在动粒上的动力学控制着两个关键的有丝分裂过程：最初建立正确的动粒-微管连接，随后沉默纺锤体检查点。
