title: The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase.
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 dynein-dynactin complex removes spindle checkpoint proteins from kinetochores to facilitate the transition to anaphase. Three components (p150(Glued), 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 p150(Glued) 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 p150(Glued) 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.
authors.affiliation: Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsui
authors.forename: Akiko
authors.initials: A
authors.lastname: Nagamachi
authors.forename: Hiroya
authors.initials: H
authors.lastname: Asou
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aki
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inaba
mesh_terms: D000705:Anaphase / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism*; D043171:Chromosomal Instability / Q000502:physiology; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: C000606360:DCTN1 protein, human; C000606361:DCTN2 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins