Mishima Lab

Research Summary

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).

Selected Publications

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. doi: 10.1182/blood-2012-10-461392 PubMed

Lee, K.Y., Davies, T. and Mishima, M. (2012)
Cytokinesis microtubule organisers at a glance. J Cell Sci. 125:3495-500 Pubmed

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 Pubmed

Douglas, M. E. and Mishima, M. (2010)
Still entangled: assembly of the central spindle by multiple microtubule modulators. Semin Cell Dev Biol. 21:899-908 Pubmed

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 Pubmed

Lab Members and Projects

	Mishan Britto \| Research Fellow I want to understand the mechanistic & biochemical role of Cyk-4 and Zen-4 in the central spindle & midbody. I use mechanochemical tools on modified in-vitro surfaces towards this. Furthermore, I am creating stable human cell lines to put these studies in perspective.
	Behrooz Esmaeili \| Research Fellow My aim is to reveal the molecular mechanisms of central spindle formation by a genetic approach using C. elegans as a model system.
	Antonia Sagona \| EMBO Fellow My aim is to characterise the function of a protein kinase isolated in a forward genetic screen for genes regulating mechanical robustness of the central spindle