The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells

Ryota Uehara, Ryu Suke Nozawa, Akiko Tomioka, Sabine Petry, Ronald D. Vale, Chikashi Obuse, Gohta Goshima

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

The mitotic spindle is constructed from microtubules (MTs) nucleated from centrosomes, chromosome proximal regions, and preexisting spindle MTs. Augmin, a recently identified protein complex, is a critical factor in spindle MT-based MT generation in Drosophila S2 cells. Previously, we identified one subunit of human augmin. Here, by using mass spectrometry, we identified the full human augmin complex of 8 subunits and show that it interacts with the γ-tubulin ring complex (γ-TuRC). Unlike augmin-depleted S2 cells, in which the defect in spindle-mediated MT generation is mostly compensated by centrosomal MTs, augmin knockdown alone in HeLa cells triggers the spindle checkpoint, reduces tension on sister kinetochores, and severely impairs metaphase progression. Human augmin knockdown also reduces the number of central spindle MTs during anaphase and causes late-stage cytokinesis failure. A link between augmin and γ-TuRC is likely critical for these functions, because a γ-TuRC mutant that attenuates interaction with augmin does not restore function in vivo. These results demonstrate that MT generation mediated by augmin and γs critical for chromosome segregation and cytokinesis in human cells.

Original languageEnglish (US)
Pages (from-to)6998-7003
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number17
DOIs
StatePublished - Apr 28 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Centrosome
  • Mitosis
  • RNAi
  • Spindle checkpoint

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