Importin α phosphorylation promotes TPX2 activation by GM130 to control astral microtubules and spindle orientation

被引：13

作者：

Guo, Haijing ^{[1
]}

Wei, Jen-Hsuan ^{[2
]}

Zhang, Yijun ^{[1
]}

Seemann, Joachim ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA

[2] Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan

来源：

JOURNAL OF CELL SCIENCE | 2021年 / 134卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Mitosis; Astral microtubules; Spindle orientation; TPX2; Importin alpha; GM130; CDK1; Phosphorylation; Golgi; GOLGI-APPARATUS; CELL-DIVISION; PROTEIN; AURORA; DIFFERENTIATION; INHERITANCE; MITOSIS; MECHANISMS; COMPONENTS; REGULATOR;

D O I：

10.1242/jcs.258356

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The orientation of the spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates astral microtubules. TPX2 in the spindle pole area is activated by GM130 (GOLGA2) on Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin alpha 1 (KPNA2) binding. Mitotic phosphorylation of importin a at serine 62 (S62) by CDK1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin alpha S62A mutation impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130-importin alpha-TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin a is regulated by CDK1-mediated phosphorylation.

引用

页数：13