Martino Lisa, Morchoisne-Bolhy Stéphanie, Cheerambathur Dhanya K, Van Hove Lucie, Dumont Julien, Joly Nicolas, Desai Arshad, Doye Valérie, Pintard Lionel
Cell Cycle and Development, Institut Jacques Monod, UMR7592 CNRS - Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Non-conventional Functions of Nuclear Pore, Institut Jacques Monod, UMR7592 CNRS - Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Dev Cell. 2017 Oct 23;43(2):157-171.e7. doi: 10.1016/j.devcel.2017.09.019.
In animal cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Whereas mitotic kinases have been implicated in NEBD, how they coordinate their activity to trigger this event is unclear. Here, we show that both in human cells and Caenorhabditis elegans, the Polo-like kinase 1 (PLK-1) is recruited to the nuclear pore complexes, just prior to NEBD, through its Polo-box domain (PBD). We provide evidence that PLK-1 localization to the nuclear envelope (NE) is required for efficient NEBD. We identify the central channel nucleoporins NPP-1/Nup58, NPP-4/Nup54, and NPP-11/Nup62 as the critical factors anchoring PLK-1 to the NE in C. elegans. In particular, NPP-1, NPP-4, and NPP-11 primed at multiple Polo-docking sites by Cdk1 and PLK-1 itself physically interact with the PLK-1 PBD. We conclude that nucleoporins play an unanticipated regulatory role in NEBD, by recruiting PLK-1 to the NE thereby facilitating phosphorylation of critical downstream targets.
在动物细胞中，正确的染色体分离需要核膜破裂（NEBD）。虽然有丝分裂激酶与核膜破裂有关，但它们如何协调活性以触发这一事件尚不清楚。在这里，我们表明，在人类细胞和秀丽隐杆线虫中，就在核膜破裂之前，Polo样激酶1（PLK-1）通过其Polo盒结构域（PBD）被招募到核孔复合体。我们提供的证据表明，PLK-1定位于核膜（NE）是有效核膜破裂所必需的。我们确定中心通道核孔蛋白NPP-1/Nup58、NPP-4/Nup54和NPP-11/Nup62是将PLK-1锚定在秀丽隐杆线虫核膜上的关键因素。特别是，由Cdk1和PLK-1自身在多个Polo停靠位点引发的NPP-1、NPP-4和NPP-11与PLK-1的PBD发生物理相互作用。我们得出结论，核孔蛋白在核膜破裂中发挥了意想不到的调节作用，通过将PLK-1招募到核膜上，从而促进关键下游靶点的磷酸化。
