Cell Biology Program, Institut Jacques Monod, UMR 7592 Centre National de la Recherche Scientifique-Université Paris Diderot, 75205 Paris Cedex 13, France.
J Cell Biol. 2011 Mar 7;192(5):855-71. doi: 10.1083/jcb.201007118.
Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2-BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly.
中心体在整个细胞周期中与核膜（NE）密切相关，在前期，当它们分离以建立未来的有丝分裂纺锤体时，这种联系得以维持。在这个阶段，着丝粒成分 CENP-F、NudE、NudEL、动力蛋白和动力蛋白激活蛋白在 NE 处积累。在这里，我们证明了核孔复合物（NPC）蛋白 Nup133 的 N 端结构域虽然对 NPC 组装在很大程度上是可有可无的，但对于在前期将动力蛋白/动力蛋白激活蛋白复合物有效地锚定到 NE 是必需的。Nup133 通过 CENP-F 和 NudE/EL 的相互作用网络发挥此功能。我们表明，这条分子链对于维持有丝分裂进入时中心体与 NE 的关联至关重要，并且在不干扰先前描述的 RanBP2-BICD2 依赖性中心体锚定途径的情况下促进此过程。最后，我们的研究揭示了在 G2/M 转换时将中心体系绳到核表面，与其他细胞机制一起，有助于双极纺锤体组装的早期阶段。
