Search A-Z index Contact
University of Cambridge Home Dr Masanori Mishima
University of Cambridge >  School of the Biological Sciences  >  Department of Biochemistry spacerStaff email list spacerPhone
 
Research Groups
 
Service & Research Support
Facilities
 
Past members
last known active weblink
 

 

 

 

Dr Mishima

Molecular mechanism of cytokinesis

cytokinesisResearch Groupings: Cancer | Structural and molecular cell biology

Cytokinesis is essential for cell proliferation. Failure of cytokinesis leads to aneuploidy or chromosomal instability, which has been associated with human cancers. Successful cytokinesis relies on a dynamic interplay between microtubules, the actin cytoskeleton, and membrane compartments under the control of the cell cycle machinery. In spite of its importance, the molecular mechanism of cytokinesis in animal cells has not yet been fully clarified.

We would like to better understand cytokinesis in terms of dynamic assembly of molecular machinery. 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 have crucial roles through all the steps of cytokinesis from initiation to completion. We will address the following questions.

  • How is the central spindle/midbody assembled?
  • How does the central spindle/midbody contribute to the progression of cytokinesis at the molecular level?

We will focus on centralspindlin, a stable protein complex of a mitotic kinesin-like protein and a Rho-family GTPase-activating protein (RhoGAP), which is crucial for assembly of the central spindle and the midbody. We will characterise the dynamic behaviour of centralspindlin and investigate centralspindlin-interacting proteins by using mammalian cultured cells and C. elegans embryos as model systems. In addition to biochemical and genetical analyses, live imaging both at single molecule level in vitro and at subcellular level in vivo will be performed. We will also develop experimental strategies to (in)activate molecules of interest in vivo in a reasonable time resolution to dissect the molecular mechanism of cytokinesis.

References

  1. Guse A, Mishima M and Glotzer MA (2005) Conserved role for Aurora B phosphorylation of ZEN-4/MKLP1 in completion of cytokinesis. Curr. Biol. 15, 778-86
  2. Mishima M, Pavicic V, Grüneberg U, Nigg EA, and Glotzer M (2004) Cell cycle regulation of central spindle assembly. Nature 430, 908-13
  3. Mishima M, Kaitna S and Glotzer M (2002) Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev. Cell 2, 41-54.

Valid XHTML 1.0!