title: Nuclear Mitotic Apparatus (NuMA) Interacts with and Regulates Astrin at the Mitotic Spindle.
abstract: The large nuclear mitotic apparatus (NuMA) protein is an essential player in mitotic spindle assembly and maintenance. We report here the identification of Astrin, a spindle- and kinetochore-associated protein, as a novel interactor of NuMA. We show that the C-terminal tail of NuMA can directly bind to the C terminus of Astrin and that this interaction helps to recruit Astrin to microtubules. Knockdown of NuMA by RNA interference dramatically impaired Astrin recruitment to the mitotic spindle. Overexpression of the N terminus of mammalian homologue of Drosophila Pins (LGN), which blocks the microtubule binding of NuMA and competes with Astrin for NuMA binding, also led to similar results. Furthermore, we found that cytoplasmic dynein is required for the spindle pole accumulation of Astrin, and dynein-mediated transport is important for balanced distribution of Astrin between spindle poles and kinetochores. On the other hand, if Astrin levels are reduced, then NuMA could not efficiently concentrate at the spindle poles. Our findings reveal a direct physical link between two important regulators of mitotic progression and demonstrate the critical role of the NuMA-Astrin interaction for accurate cell division.
authors.affiliation: From the Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912 xichu@augusta.edu.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chu
authors.affiliation: From the Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912.
authors.forename: Xuanyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: From the Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Wan
authors.affiliation: From the Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: From the Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912 qdu@augusta.edu.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Du
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004331:Drosophila melanogaster; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; C486663:SPAG5 protein, human; D004398:Dyneins
keywords: Astrin; NuMA; chromosomes; microtubule; mitosis; mitotic spindle; protein-protein interaction