The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells
The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells
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DOI：
10.1101/gad.245603
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发表时间：
2003-02-01
影响因子：
10.5
通讯作者：
Raff, JW
中科院分区：
文献类型：
--
作者：
Gergely, F;Draviam, VM;Raff, JW
ch-TOG/XMAP 215蛋白家族直接与微管结合，似乎在稳定纺锤体微管中发挥重要作用。这些蛋白质主要通过影响微管正端动力学来稳定微管，然而，在体内，它们都强烈地集中在纺锤体极点，微管的负端集中在那里。在果蝇胚胎中，需要中心体蛋白D-TACC来有效地将ch-TOG/Msps募集到中心体。在人类中，ch-TOG和三种已知的TACC蛋白与癌症有关，但它们的功能尚不清楚。在这里，我们使用RNA干扰从HeLa细胞中广泛地耗尽TACC 3和ch-TOG。在TACC 3缺失的细胞中，纺锤体组织良好，但微管部分不稳定，ch-TOG不再集中在纺锤体微管上。在ch-TOG耗尽的细胞中，形成相对坚固的纺锤体，但纺锤体高度紊乱。因此，在人类体细胞中，ch-TOG似乎在组织纺锤体极中起主要作用，并且在稳定纺锤体微管中起更次要的作用，所述稳定纺锤体微管至少部分地通过与TACC 3的相互作用介导。
The ch-TOG/XMAP215 family of proteins bind directly to microtubules and appear to play an essential role in stabilizing spindle microtubules. These proteins stabilize microtubules mainly by influencing microtubule plus-end dynamics, yet, in vivo, they are all strongly concentrated at spindle poles, where the minus ends of the microtubules are concentrated. In Drosophila embryos, the centrosomal protein D-TACC is required to efficiently recruit ch-TOG/Msps to centrosomes. In humans, ch-TOG and the three known TACC proteins have been implicated in cancer, but their functions are unknown. Here we extensively depleted TACC3 and ch-TOG from HeLa cells using RNA interference. In TACC3-depleted cells, spindles are well organized, but microtubules are partially destabilized and ch-TOG is no longer concentrated on spindle microtubules. in ch-TOG-depleted cells, relatively robust spindles form, but the spindles are highly disorganized. Thus, in human somatic cells, ch-TOG appears to play a major role in organizing spindle poles, and a more minor role in stabilizing spindle microtubules that is, at least in part, mediated via an interaction with TACC3.