Mutual dependence of Mob1 and the chromosomal passenger complex for localization during mitosis

• Published in: Molecular biology of the cell Vol. 21; no. 3; pp. 380 - 392
• Main Authors: Wilmeth, Lori Jo, Shrestha, Sanjay, Montaño, Gilbert, Rashe, Jennifer, Shuster, Charles Bradley
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01-02-2010
• Subjects: Adaptor Proteins, Signal Transducing - classification; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Animals; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosome Segregation; Cytokinesis - physiology; HeLa Cells; Humans; Kinesins - genetics; Kinesins - metabolism; Kinetochores - metabolism; Macromolecular Substances - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Mitosis - physiology; Molecular Sequence Data; Phylogeny; Polo-Like Kinase 1; Protein Isoforms - classification; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Sequence Alignment; Signal Transduction - physiology; Spindle Apparatus - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.e09-06-0471

The spatial and temporal coordination of chromosome segregation with cytokinesis is essential to ensure that each daughter cell receives the correct complement of chromosomal and cytoplasmic material. In yeast, mitotic exit and cytokinesis are coordinated by signaling cascades whose terminal components include a nuclear Dbf2-related family kinase and a noncatalytic subunit, Mps one binding (Mob) 1. There are five human Mob1 isoforms, all of which display redundant localization patterns at the spindle poles and kinetochores in early mitosis, and the spindle midzone during cytokinesis. Mob1 shares similar localization patterns to Polo-like kinase (Plk1) and the chromosomal passenger complex (CPC), and although depletion of Plk1 resulted in a loss of Mob1 from the spindle poles, Mob1 recruitment to kinetochores was unaffected. Conversely, disruption of CPC signaling resulted in a loss of Mob1 from kinetochores without disrupting recruitment to the spindle poles. In Mob1-depleted cells, the relocalization of the CPC and mitotic kinesin-like protein (MKLP) 2 to the spindle midzone was delayed during early anaphase, and as a consequence, the midzone recruitment of MKLP1 also was affected. Together, these results suggest that Mob1 and the other mammalian orthologues of the mitotic exit network regulate mitotic progression by facilitating the timely mobilization of the CPC to the spindle midzone.