Research projects
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 understand cytokinesis more fully, 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 Caenorhabditis 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.
