Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis.
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.
Aumais
Jonathan P
JP
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Williams
Shelli N
SN
Luo
Weiping
W
Nishino
Michiya
M
Caldwell
Kim A
KA
Caldwell
Guy A
GA
Lin
Sue-Hwa
SH
Yu-Lee
Li-Yuan
LY
D021581:Active Transport, Cell Nucleus; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans; D018797:Cell Cycle Proteins; D002455:Cell Division; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D015536:Down-Regulation; D004398:Dyneins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012313:RNA / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D004398:Dyneins; D005656:Fungal Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012313:RNA; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C094005:NUDC protein, Emericella nidulans