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First published online 1 April 2003
doi: 10.1242/jcs.00412
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Research Article |
1 Department of Molecular and Cellular Biology, Baylor College of Medicine, One
Baylor Plaza, Houston, Texas 77030, USA
2 Department of Biological Sciences, The University of Alabama, Tuscaloosa,
Alabama 35487, USA
3 Department of Molecular Pathology, MD Anderson Cancer Center, Houston, Texas
77030, USA
4 Program in Cell and Molecular Biology, Baylor College of Medicine, One Baylor
Plaza, Houston, Texas 77030, USA
5 Department of Immunology, Baylor College of Medicine, One Baylor Plaza,
Houston, Texas 77030, USA
6 Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston,
Texas 77030, USA
* Author for correspondence (e-mail: yulee{at}bcm.tmc.edu)
Accepted 5 February 2003
NudC, a nuclear movement protein that associates with dynein, was originally cloned as a mitogen-inducible early growth response gene. NudC forms a biochemical complex with components of the dynein/dynactin complex and is suggested to play a role in translocation of nuclei in proliferating neuronal progenitors as well as in migrating neurons in culture. Here, we show that NudC plays multiple roles in mitosis and cytokinesis in cultured mammalian cells. Altering NudC levels by either small interfering RNA-mediated gene silencing or adenovirus-mediated overexpression resulted in multinucleated cells and cells with persistent intercellular connections and disorganized midzone and midbody matrix. These phenotypes suggest a failure in cytokinesis in NudC altered cells. Further, a key mitotic enzyme, polo-like kinase, is mislocalized from the centrosomes and the midbody in NudC altered cells. Gene silencing of nud-1, the Caenorhabditis elegans ortholog of NudC, led to a loss of midzone microtubules and the rapid regression of the cleavage furrow, which resulted in one-celled embryos containing two nuclei. The loss of midzone microtubule organization owing to silencing of the NudC/nud-1 gene in two systems, coupled with the loss of Plk1 from mitotic structures in mammalian cells, provide clues to the cytokinesis defect and the multinucleation phenotype. Our findings suggest that NudC functions in mitosis and cytokinesis, in part by regulating microtubule organization at the midzone and midbody.
Key words: NudC, Plk1, Cytokinesis, Midbody microtubule, Small interfering RNA, Caenorhabditis elegans
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