Ozlü Nurhan, Srayko Martin, Kinoshita Kazuhisa, Habermann Bianca, O'toole Eileen T, Müller-Reichert Thomas, Schmalz Natalie, Desai Arshad, Hyman Anthony A
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden 01307, Germany.
Dev Cell. 2005 Aug;9(2):237-48. doi: 10.1016/j.devcel.2005.07.002.
In vertebrates, the microtubule binding protein TPX2 is required for meiotic and mitotic spindle assembly. TPX2 is also known to bind to and activate Aurora A kinase and target it to the spindle. However, the relationship between the TPX2-Aurora A interaction and the role of TPX2 in spindle assembly is unclear. Here, we identify TPXL-1, a C. elegans protein that is the first characterized invertebrate ortholog of TPX2. We demonstrate that an essential role of TPXL-1 during mitosis is to activate and target Aurora A to microtubules. Our data suggest that this targeting stabilizes microtubules connecting kinetochores to the spindle poles. Thus, activation and targeting of Aurora A appears to be an ancient and conserved function of TPX2 that plays a central role in mitotic spindle assembly.
在脊椎动物中，微管结合蛋白TPX2是减数分裂和有丝分裂纺锤体组装所必需的。已知TPX2还能结合并激活极光激酶A（Aurora A kinase），并将其靶向至纺锤体。然而，TPX2与极光激酶A的相互作用以及TPX2在纺锤体组装中的作用之间的关系尚不清楚。在此，我们鉴定出了TPXL-1，这是一种秀丽隐杆线虫蛋白，是首个被表征的TPX2的无脊椎动物直系同源物。我们证明，TPXL-1在有丝分裂过程中的一个重要作用是激活极光激酶A并将其靶向至微管。我们的数据表明，这种靶向作用稳定了连接动粒与纺锤体极的微管。因此，极光激酶A的激活和靶向作用似乎是TPX2古老且保守的功能，在有丝分裂纺锤体组装中起核心作用。
