Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis.

Jonathan P Aumais,Sue-Hwa Lin,Shelli N Williams,Li-Yuan Yu-Lee,Weiping Luo,Guy A Caldwell,Kim A Caldwell,Michiya Nishino

doi:10.1242/jcs.00412

Abstract

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.

Highlights

NudC was first identified as a gene that regulates nuclear movement in the asexual reproductive cycle of the filamentous fungus Aspergillus nidulans
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

Summary

Introduction

NudC was first identified as a gene that regulates nuclear movement in the asexual reproductive cycle of the filamentous fungus Aspergillus nidulans. The functional interactions between NudC, Lis, NudeL/NudE and dynein/dynactin are likely to contribute to motor functions and microtubule dynamics during such diverse cellular processes as nuclear movement (Xiang et al, 1994; Morris et al, 1998; Aumais et al, 2001), neuronal migration (Niethammer et al, 2000; Sasaki et al, 2000; Smith et al, 2000; Leventer et al, 2001; Aumais et al, 2001; Faulkner et al, 2000; Vallee et al, 2000), axonal transport (Liu et al, 2000), intracellular transport (Karki et al, 1998; Karki and Holzbaur, 1999; Swan et al, 1999) and cell division (Faulkner et al, 2000; Tai et al, 2002; Coquelle et al, 2002; Zhang et al, 2002; Liu et al, 1999; Liu et al, 2000)

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