Aurora A activates D-TACC-Msps complexes exclusively at centrosomes to stabilize centrosomal microtubules.

Aurora A activates D-TACC-Msps complexes exclusively at centrosomes to stabilize centrosomal microtubules.
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DOI:
10.1083/jcb.200504097
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发表时间:
2005-09-26
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Raff JW
Raff JW
中科院分区:
其他
文献类型:
--
作者:
Barros TP;Kinoshita K;Hyman AA;Raff JW

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中心体是动物细胞有丝分裂过程中微管(MT)组装的主要场所,但目前尚不清楚这是如何实现的。转化酸性卷曲螺旋(TACC)蛋白在有丝分裂期间通过将小孢子(Msps)/XMAP 215蛋白募集到中心体来稳定MT。TACC蛋白可以在体外被Aurora A激酶磷酸化,但其意义尚不清楚。我们发现,果蝇TACC(D-TACC)的Ser 863磷酸化只在中心体在有丝分裂过程中的极光A-依赖的方式。在仅表达不能在Ser 863(GFP-S863 L)上磷酸化的D-TACC的突变形式的胚胎中,纺锤体MT部分不稳定,而星形MT显著不稳定。GFP-S863 L主要集中在中心体,并在中心体募集Msps,但不能与MT的负端结合。我们认为中心体丝氨酸863上的D-TACC磷酸化允许D-TACC-Msps复合物稳定中心体相关MT的负端。这可能解释了为什么中心体是有丝分裂过程中MT组装的优势位点。
Centrosomes are the dominant sites of microtubule (MT) assembly during mitosis in animal cells, but it is unclear how this is achieved. Transforming acidic coiled coil (TACC) proteins stabilize MTs during mitosis by recruiting Minispindles (Msps)/XMAP215 proteins to centrosomes. TACC proteins can be phosphorylated in vitro by Aurora A kinases, but the significance of this remains unclear. We show that Drosophila melanogaster TACC (D-TACC) is phosphorylated on Ser863 exclusively at centrosomes during mitosis in an Aurora A–dependent manner. In embryos expressing only a mutant form of D-TACC that cannot be phosphorylated on Ser863 (GFP-S863L), spindle MTs are partially destabilized, whereas astral MTs are dramatically destabilized. GFP-S863L is concentrated at centrosomes and recruits Msps there but cannot associate with the minus ends of MTs. We propose that the centrosomal phosphorylation of D-TACC on Ser863 allows D-TACC–Msps complexes to stabilize the minus ends of centrosome-associated MTs. This may explain why centrosomes are such dominant sites of MT assembly during mitosis.
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