Cytokinesis is essential for cell proliferation. Its failure leads to aneuploidy, which is often associated with cancer. In spite of its importance, the molecular mechanism of cytokinesis has not yet been fully clarified. We would like to understand cytokinesis more fully, in terms of how molecular machines assemble dynamically. The central spindle is a microtubule-based molecular assembly that forms between the segregating chromosomes during anaphase. During telophase, it associates with the ingressing cleavage furrow and matures into the midbody. These microtubule-based structures play crucial roles in all stages of cytokinesis from initiation to completion. We will address the following questions:
1) How is the central spindle/midbody assembled?
2) How does the central spindle/midbody contribute to the progression of cytokinesis?
To address these questions, we have been combining various approaches including genetics in Caenorhabditis elegans , biochemistry and live observation in mammalian cultured cells and observation at the single molecule level by total internal reflection fluorescence microscopy (TIRF).
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Lee, K.-Y., Esmaeili, B., Zealley, B., & Mishima, M. (2015)
Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle. Nature Communications, 6, 7290.
Davies, T., Kodera, N., Kaminski Schierle, G. S., Rees, E., Erdelyi, M., Kaminski, C. F., et al. (2015)
CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation. PLoS Biology, 13(4), e1002121.
Liljeholm M., Irvine A. F., Vikberg A. L., Norberg A., Month S., Sandström H., Wahlin A., Mishima M., Golovleva I. (2013)
Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23. Blood 121:4791-9.
Lee, K.-Y., Davies, T. and Mishima, M. (2012)
Cytokinesis microtubule organisers at a glance. J Cell Sci, 125:3495-500.
Joseph, N., Hutterer, A., Poser, I. and Mishima, M. (2012)
ARF6 GTPase protects the post-mitotic midbody from 14-3-3-mediated disintegration. EMBO J, 31:2604-14.
Douglas, M. E. and Mishima M. (2010)
Still entangled: assembly of the central spindle by multiple microtubule modulators. Semin Cell Dev Biol, 21:899-08.
Douglas, M. E., Davies, T., Joseph, N. and Mishima M. (2010)
Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis. Curr Biol, 20:927-33.
Hutterer A., Glotzer M. and Mishima M. (2009)
Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody. Curr Biol, 15:2043-9.
My aim is to understand how centralspindlin and other microtubule bundling proteins cooperate to form the central spindle in human cells.
My aim is to reveal the molecular mechanisms of central spindle formation by a genetic approach using C. elegans as a model system.