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Free keywords:
Animals
Antigens, Nuclear/genetics/metabolism
Centrosome/*metabolism
Drosophila Proteins/genetics/metabolism
Drosophila melanogaster/metabolism
HeLa Cells
Humans
Microtubule-Associated Proteins/genetics/*metabolism
Microtubules/metabolism
Multiprotein Complexes/*metabolism
Nuclear Matrix-Associated Proteins/genetics/metabolism
Protein Subunits/*metabolism
RNA Interference
Recombinant Fusion Proteins/genetics/metabolism
Spindle Apparatus/*metabolism
Tubulin/genetics/metabolism
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.
