Schlaitz Anne-Lore, Srayko Martin, Dammermann Alexander, Quintin Sophie, Wielsch Natalie, MacLeod Ian, de Robillard Quentin, Zinke Andrea, Yates John R, Müller-Reichert Thomas, Shevchenko Andrei, Oegema Karen, Hyman Anthony A
Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Cell. 2007 Jan 12;128(1):115-27. doi: 10.1016/j.cell.2006.10.050.
Microtubule behavior changes during the cell cycle and during spindle assembly. However, it remains unclear how these changes are regulated and coordinated. We describe a complex that targets the Protein Phosphatase 2A holoenzyme (PP2A) to centrosomes in C. elegans embryos. This complex includes Regulator of Spindle Assembly 1 (RSA-1), a targeting subunit for PP2A, and RSA-2, a protein that binds and recruits RSA-1 to centrosomes. In contrast to the multiple functions of the PP2A catalytic subunit, RSA-1 and RSA-2 are specifically required for microtubule outgrowth from centrosomes and for spindle assembly. The centrosomally localized RSA-PP2A complex mediates these functions in part by regulating two critical mitotic effectors: the microtubule destabilizer KLP-7 and the C. elegans regulator of spindle assembly TPXL-1. By regulating a subset of PP2A functions at the centrosome, the RSA complex could therefore provide a means of coordinating microtubule outgrowth from centrosomes and kinetochore microtubule stability during mitotic spindle assembly.
微管行为在细胞周期和纺锤体组装过程中会发生变化。然而，这些变化是如何被调控和协调的仍不清楚。我们描述了一种在秀丽隐杆线虫胚胎中将蛋白磷酸酶2A全酶（PP2A）靶向中心体的复合物。该复合物包括纺锤体组装调节因子1（RSA-1），它是PP2A的一个靶向亚基，以及RSA-2，一种结合并将RSA-1招募到中心体的蛋白质。与PP2A催化亚基的多种功能不同，RSA-1和RSA-2是中心体微管生长和纺锤体组装所特需的。定位于中心体的RSA-PP2A复合物部分地通过调控两个关键的有丝分裂效应器来介导这些功能：微管去稳定剂KLP-7和秀丽隐杆线虫纺锤体组装调节因子TPXL-1。因此，通过在中心体调节PP2A功能的一个子集，RSA复合物可以提供一种在有丝分裂纺锤体组装过程中协调中心体微管生长和动粒微管稳定性的方式。
