HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity

被引：203

作者：

Lawo, Steffen ^{[1
,2
]}

Bashkurov, Mikhail ^{[1
]}

Mullin, Michael ^{[1
]}

Ferreria, Mariana Gomez ^{[1
]}

Kittler, Ralf ^{[3
]}

Habermann, Bianca ^{[4
]}

Tagliaferro, Andrea ^{[1
]}

Poser, Ina ^{[4
]}

Hutchins, James R. A. ^{[5
]}

Hegemann, Bjoern ^{[5
]}

Pinchev, Deborah ^{[1
]}

BuchholZ, Frank ^{[4
]}

Peters, Jan-Michael ^{[5
]}

Hyman, Anthony A. ^{[4
]}

Gingras, Anne-Claude ^{[1
,2
]}

Pelletier, Laurence ^{[1
,2
]}

机构：

[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[2] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[3] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[4] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany

[5] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria

来源：

CURRENT BIOLOGY | 2009年 / 19卷 / 10期

关键词：

MITOTIC SPINDLE; HUMAN-CELLS; MICROTUBULE AMPLIFICATION; CENTRIOLE DUPLICATION; MAMMALIAN-CELLS; C-ELEGANS; PROTEIN; NUMA; MITOSIS; MECHANISMS;

D O I：

10.1016/j.cub.2009.04.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: The assembly of a robust microtubule-based mitotic spindle is a prerequisite for the accurate segregation of chromosomes to progeny. Spindle assembly relies on the concerted action of centrosomes, spindle microtubules, molecular motors, and nonmotor spindle proteins. Results: Here we use an RNA-interference screen of the human centrosome proteome to identify novel regulators of spindle assembly. One such regulator is HAUS, an 8-subunit protein complex that shares homology to Drosophila Augmin. HAUS localizes to interphase centrosomes and to mitotic spindle microtubules, and its disruption induces microtubule-dependent fragmentation of centrosomes along with an increase in centrosome size. HAUS disruption results in the destabilization of kinetochore microtubules and the eventual formation of multipolar spindles. These severe mitotic defects are alleviated by codepletion of NuMA, indicating that both factors regulate opposing activities. HAUS disruption alters NuMA localization, suggesting that mislocalized NuMA activity contributes to the spindle and centrosome defects observed. Conclusion: The human Augmin complex (HAUS) is a critical and evolutionary conserved multisubunit protein complex that regulates centrosome and spindle integrity.

引用

页码：816 / 826

页数：11

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