title: Systematic dissection of dynein regulators in mitosis.
abstract: Cytoplasmic dynein is a large minus end-directed motor complex with multiple functions during cell division. The dynein complex interacts with various adaptor proteins, including the dynactin complex, thought to be critical for most dynein functions. Specific activities have been linked to several subunits and adaptors, but the function of the majority of components has remained elusive. Here, we systematically address the function of each dynein-dynactin subunit and adaptor protein in mitosis. We identify the essential components that are required for all mitotic functions of dynein. Moreover, we find specific dynein recruitment factors, and adaptors, like Nde1/L1, required for activation, but largely dispensable for dynein localization. Most surprisingly, our data show that dynactin is not required for dynein-dependent spindle organization, but acts as a dynein recruitment factor. These results provide a comprehensive overview of the role of dynein subunits and adaptors in mitosis and reveal that dynein forms distinct complexes requiring specific recruiters and activators to promote orderly progression through mitosis.
authors.affiliation: Department of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Jonne A
authors.initials: JA
authors.lastname: Raaijmakers
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Tanenbaum
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
mesh_terms: D001696:Biomechanical Phenomena; D018385:Centrosome / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D009685:Nuclear Envelope / Q000378:metabolism; D011418:Prophase; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; D034741:RNA, Small Interfering; D004398:Dyneins