Mammalian RanBP1 regulates centrosome cohesion during mitosis
Mammalian RanBP1 regulates centrosome cohesion during mitosis
复制标题
DOI：
10.1242/jcs.00624
复制
发表时间：
2003-08-15
影响因子：
4
通讯作者：
Lavia, P
中科院分区：
文献类型：
--
作者：
Di Fiore, B;Ciciarello, M;Lavia, P
Ran GT3在间期核质转运的调控中起着重要作用。在非洲爪蟾卵母细胞提取物中，Ran的有丝分裂作用也得到了证实。在该系统中，Ran-GTP（Ran的RCC 1交换因子）通过调节“aster促进活动”的可用性来驱动纺锤体组件。在以前的研究中，以评估是否Ran网络也影响哺乳动物细胞中的有丝分裂，我们发现，Ran结合蛋白1（RanBP 1），Ran的主要效应物，过表达诱导多极纺锤体。我们现在发现这些异常纺锤体是通过有丝分裂中心体内聚性的丧失而产生的。具体而言，RanBP 1过量诱导分裂的母亲和女儿的中心粒在纺锤体极;所产生的分裂中心粒可以单独组织功能性微管阵列，从而产生功能性纺锤体极。RanBP 1依赖的中心体分裂在有丝分裂中特异性诱导，并且需要微管完整性和Eg 5活性。此外，我们已经确定了RanBP 1在中心体的一部分。这些数据表明，过表达的RanBP 1干扰了在有丝分裂过程中控制中心体结构和动力学特征的关键因子，并有助于揭示Ran网络下游的新的有丝分裂功能。
The Ran GTPase plays a central function in control of nucleo-cytoplasmic transport in interphase. Mitotic roles of Ran have also been firmly established in Xenopus oocyte extracts. In this system, Ran-GTP, or the RCC1 exchange factor for Ran, drive spindle assembly by regulating the availability of 'aster-promoting activities'. In previous studies to assess whether the Ran network also influences mitosis in mammalian cells, we found that overexpression of Ran-binding protein 1 (RanBP1), a major effector of Ran, induces multipolar spindles. We now show that these abnormal spindles are generated through loss of cohesion in mitotic centrosomes. Specifically, RanBP1 excess induces splitting of mother and daughter centrioles at spindle poles; the resulting split centrioles can individually organize functional microtubule arrays, giving rise to functional spindle poles. RanBP1-dependent centrosome splitting is specifically induced in mitosis and requires microtubule integrity and Eg5 activity. In addition, we have identified a fraction of RanBP1 at the centrosome. These data indicate that overexpressed RanBP1 interferes with crucial factor(s) that control structural and dynamic features of centrosomes during mitosis and contribute to uncover novel mitotic functions downstream of the Ran network.