HURP permits MTOC sorting for robust meiotic spindle bipolarity, similar to extra centrosome clustering in cancer cells

被引:87
作者
Breuer, Manuel [1 ]
Kolano, Agnieszka [1 ]
Kwon, Mijung [2 ]
Li, Chao-Chin [3 ,4 ]
Tsai, Ting-Fen [3 ,4 ]
Pellman, David [2 ]
Brunet, Stephane [1 ]
Verlhac, Marie-Helene [1 ]
机构
[1] Univ Paris 06, CNRS, Unite Mixte Rech 7622, F-75005 Paris, France
[2] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Natl Yang Ming Univ, Dept Life Sci, Taipei 112, Taiwan
[4] Natl Yang Ming Univ, Inst Genome Sci, Taipei 112, Taiwan
关键词
MOUSE OOCYTES; MICROTUBULE ORGANIZATION; HEPATOCELLULAR-CARCINOMA; METAPHASE SPINDLE; MEIOSIS-I; CHROMOSOMES; DYNAMICS; DIVISION; ROLES; MOTOR;
D O I
10.1083/jcb.201005065
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In contrast to somatic cells, formation of acentriolar meiotic spindles relies on the organization of microtubules (MTs) and MT-organizing centers (MTOCs) into a stable bipolar structure. The underlying mechanisms are still unknown. We show that this process is impaired in hepatoma up-regulated protein (Hurp) knockout mice, which are viable but female sterile, showing defective oocyte divisions. HURP accumulates on interpolar MTs in the vicinity of chromosomes via Kinesin-5 activity. By promoting MT stability in the spindle central domain, HURP allows efficient MTOC sorting into distinct poles, providing bipolarity establishment and maintenance. Our results support a new model for meiotic spindle assembly in which HURP ensures assembly of a central MT array, which serves as a scaffold for the genesis of a robust bipolar structure supporting efficient chromosome congression. Furthermore, HURP is also required for the clustering of extra centrosomes before division, arguing for a shared molecular requirement of MTOC sorting in mammalian meiosis and cancer cell division.
引用
收藏
页码:1251 / 1260
页数:10
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