HAUS, the 8-subunit human Augmin complex, regulates centrosome and spindle integrity
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 816-826 |
Seitenumfang | 11 |
Fachzeitschrift | Current Biology |
Jahrgang | 19 |
Ausgabenummer | 10 |
Publikationsstatus | Veröffentlicht - 26 Mai 2009 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 67349230854 |
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Schlagworte
Schlagwörter
- Animals, Antigens, Nuclear/genetics, Cell Cycle Proteins, Centrosome/metabolism, Drosophila Proteins/genetics, Drosophila melanogaster/metabolism, HeLa Cells, Humans, Microtubule-Associated Proteins/genetics, Microtubules/metabolism, Multiprotein Complexes/metabolism, Nuclear Matrix-Associated Proteins/genetics, Protein Subunits/metabolism, RNA Interference, Recombinant Fusion Proteins/genetics, Spindle Apparatus/metabolism, Tubulin/genetics