HAUS, the 8-subunit human Augmin complex, regulates centrosome and spindle integrity.
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.


CONCLUSIONS
The human Augmin complex (HAUS) is a critical and evolutionary conserved multisubunit protein complex that regulates centrosome and spindle integrity.
Lawo
Steffen
S
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Bashkurov
Mikhail
M
Mullin
Michael
M
Ferreria
Mariana Gomez
MG
Kittler
Ralf
R
Habermann
Bianca
B
Tagliaferro
Andrea
A
Poser
Ina
I
Hutchins
James R A
JR
Hegemann
Björn
B
Pinchev
Deborah
D
Buchholz
Frank
F
Peters
Jan-Michael
JM
Hyman
Anthony A
AA
Gingras
Anne-Claude
AC
Pelletier
Laurence
L
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C509189:NEDD1 protein, human; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D014404:Tubulin