Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment
Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment
复制标题
网格蛋白将磷酸化的 TACC3 招募到纺锤体极，以进行双极纺锤体组装和染色体排列
DOI：
10.1242/jcs.075911
复制
发表时间：
2010-11-01
影响因子：
4
通讯作者：
Zhang, Chuanmao
中科院分区：
文献类型：
--
作者：
Fu, Wenxiang;Tao, Wei;Zhang, Chuanmao
含酸性卷曲螺旋蛋白3（TACC3）与有丝分裂纺锤体组装有关，尽管所涉及的机制在很大程度上尚不清楚。在此我们发现网格蛋白重链（CHC）特异性结合磷酸化的TACC3，并将其募集到纺锤体极，以实现正确的纺锤体组装和染色体排列。非洲爪蟾TACC3在丝氨酸620（S620）和S626处的磷酸化，而非S33处的磷酸化，是其与CHC结合所必需的。通过RNA干扰（RNAi）敲低CHC会消除TACC3向纺锤体极的靶向定位，并导致纺锤体组装异常和染色体排列错误，这与TACC3敲低所导致的缺陷相似。此外，输入蛋白抑制CHC与磷酸化TACC3的结合，而处于GTP结合状态的GTP结合核蛋白Ran可逆转这种抑制作用。总之，这些结果表明，CHC将磷酸化的TACC3募集到纺锤体极确保了正确的纺锤体组装和染色体排列，并且这一过程受Ran调控。
Transforming acidic coiled-coil-containing protein 3 (TACC3) has been implicated in mitotic spindle assembly, although the mechanisms involved are largely unknown. Here we identify that clathrin heavy chain (CHC) binds specifically to phosphorylated TACC3 and recruits it to spindle poles for proper spindle assembly and chromosome alignment. Phosphorylation of Xenopus TACC3 at serine 620 (S620) and S626, but not S33, is required for its binding with CHC. Knockdown of CHC by RNA interference (RNAi) abolishes the targeting of TACC3 to spindle poles and results in abnormal spindle assembly and chromosome misalignment, similar to the defects caused by TACC3 knockdown. Furthermore, the binding of CHC with phosphorylated TACC3 is inhibited by importin β and this inhibition is reversed by the presence of the GTP-binding nuclear protein Ran in the GTP-bound state. Together, these results indicate that the recruitment of phosphorylated TACC3 to spindle poles by CHC ensures proper spindle assembly and chromosome alignment, and is regulated by Ran.