The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase

Yuko Ozaki, Hirotaka Matsui, Akiko Nagamachi, Hiroya Asou, Daisuke Aki, Toshiya Inaba

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The dynactin complex is required for activation of the dynein motor complex, which plays a critical role in various cell functions including mitosis. During metaphase, the dyneindynactin complex removes spindle checkpoint proteins from kinetochores to facilitate the transition to anaphase. Three components (p150Glued, dynamitin, and p24) compose a key portion of the dynactin complex, termed the projecting arm. To investigate the roles of the dynactin complex in mitosis, we used RNA interference to down-regulate p24 and p150Glued in human cells. In response to p24 down-regulation, we observed cells with delayed metaphase in which chromosomes frequently align abnormally to resemble a "figure eight," resulting in cell death. We attribute the figure eight chromosome alignment to impaired metaphasic centrosomes that lack spindle tension. Like p24, RNA interference of p150 Glued also induces prometaphase and metaphase delays; however, most of these cells eventually enter anaphase and complete mitosis. Our findings suggest that although both p24 and p150Glued components of the dynactin complex contribute to mitotic progression, p24 also appears to play a role in metaphase centrosome integrity, helping to ensure the transition to anaphase.

Original languageEnglish
Pages (from-to)5589-5598
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number7
DOIs
Publication statusPublished - 2011 Feb 18
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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