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

Steffen Lawo, Mikhail Bashkurov, Michael Mullin, Mariana Gomez Ferreria, Ralf Kittler, Bianca Habermann, Andrea Tagliaferro, Ina Poser, James R A Hutchins, Björn Hegemann, Deborah Pinchev, Frank Buchholz, Jan Michael Peters, Anthony A. Hyman, Anne Claude Gingras, Laurence Pelletier

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)816-826
Number of pages11
JournalCurrent Biology
Volume19
Issue number10
DOIs
StatePublished - May 26 2009

Fingerprint

centrosomes
Centrosome
Microtubules
microtubules
Defects
Protein Subunits
Proteome
mitotic spindle apparatus
Spindle Apparatus
Chromosomes
Proteins
RNA
Kinetochores
kinetochores
Chromosome Segregation
chromosome segregation
Interphase
protein subunits
RNA Interference
proteome

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lawo, S., Bashkurov, M., Mullin, M., Ferreria, M. G., Kittler, R., Habermann, B., ... Pelletier, L. (2009). HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity. Current Biology, 19(10), 816-826. https://doi.org/10.1016/j.cub.2009.04.033

HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity. / Lawo, Steffen; Bashkurov, Mikhail; Mullin, Michael; Ferreria, Mariana Gomez; Kittler, Ralf; Habermann, Bianca; Tagliaferro, Andrea; Poser, Ina; Hutchins, James R A; Hegemann, Björn; Pinchev, Deborah; Buchholz, Frank; Peters, Jan Michael; Hyman, Anthony A.; Gingras, Anne Claude; Pelletier, Laurence.

In: Current Biology, Vol. 19, No. 10, 26.05.2009, p. 816-826.

Research output: Contribution to journalArticle

Lawo, S, Bashkurov, M, Mullin, M, Ferreria, MG, Kittler, R, Habermann, B, Tagliaferro, A, Poser, I, Hutchins, JRA, Hegemann, B, Pinchev, D, Buchholz, F, Peters, JM, Hyman, AA, Gingras, AC & Pelletier, L 2009, 'HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity', Current Biology, vol. 19, no. 10, pp. 816-826. https://doi.org/10.1016/j.cub.2009.04.033
Lawo, Steffen ; Bashkurov, Mikhail ; Mullin, Michael ; Ferreria, Mariana Gomez ; Kittler, Ralf ; Habermann, Bianca ; Tagliaferro, Andrea ; Poser, Ina ; Hutchins, James R A ; Hegemann, Björn ; Pinchev, Deborah ; Buchholz, Frank ; Peters, Jan Michael ; Hyman, Anthony A. ; Gingras, Anne Claude ; Pelletier, Laurence. / HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity. In: Current Biology. 2009 ; Vol. 19, No. 10. pp. 816-826.
@article{32004bdd24bc42928811d24823433a2f,
title = "HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity",
abstract = "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.",
keywords = "CELLBIO",
author = "Steffen Lawo and Mikhail Bashkurov and Michael Mullin and Ferreria, {Mariana Gomez} and Ralf Kittler and Bianca Habermann and Andrea Tagliaferro and Ina Poser and Hutchins, {James R A} and Bj{\"o}rn Hegemann and Deborah Pinchev and Frank Buchholz and Peters, {Jan Michael} and Hyman, {Anthony A.} and Gingras, {Anne Claude} and Laurence Pelletier",
year = "2009",
month = "5",
day = "26",
doi = "10.1016/j.cub.2009.04.033",
language = "English (US)",
volume = "19",
pages = "816--826",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "10",

}

TY - JOUR

T1 - HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity

AU - Lawo, Steffen

AU - Bashkurov, Mikhail

AU - Mullin, Michael

AU - Ferreria, Mariana Gomez

AU - Kittler, Ralf

AU - Habermann, Bianca

AU - Tagliaferro, Andrea

AU - Poser, Ina

AU - Hutchins, James R A

AU - Hegemann, Björn

AU - Pinchev, Deborah

AU - Buchholz, Frank

AU - Peters, Jan Michael

AU - Hyman, Anthony A.

AU - Gingras, Anne Claude

AU - Pelletier, Laurence

PY - 2009/5/26

Y1 - 2009/5/26

N2 - 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.

AB - 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.

KW - CELLBIO

UR - http://www.scopus.com/inward/record.url?scp=67349230854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349230854&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2009.04.033

DO - 10.1016/j.cub.2009.04.033

M3 - Article

C2 - 19427217

AN - SCOPUS:67349230854

VL - 19

SP - 816

EP - 826

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 10

ER -