Assistant Professor, Biochemistry
Kansas State University
Roles of MyoGEF and its Interacting Partners in Cell Division and Cell Signaling (2005-2007)
Division of a cell into two daughter cells, i.e., cytokinesis, is a critical event during cell cycle progression. Failure of cytokinesis leads to the formation of multi-nucleated cells that are frequently generated during cancer development. Dr. Wei's research in part focuses is on understanding the molecular mechanism that leads to the precise positioning control of the cleavage furrow. Furrow ingression is believed to be powered by the mechanical force generated by the interaction between the filaments of the proteins actin and myosin, which form a contractile ring in anaphase and telophase cells. A body of evidence has implicated the central spindle as one of the important factors in positioning the contractile ring.
However, the underlying mechanism is still unclear: how does myosin II concentrate at the cleavage furrow in response to the assembly of the central spindle, a set of antiparallel microtubules that become bundled in anaphase cells. We have identified a novel guanine nucleotide exchange factor, MyoGEF (myosin-interacting GEF), which is capable of binding to non-muscle myosin II--concentrating at the cleavage furrow--and activating the small GTPase protein RhoA. Additionally, MyoGEF interacts with another protein, called MyoGEF-interacting central spindle protein (MICSP), which concentrates at the central spindle in anaphase cells.
We therefore hypothesize that MyoGEF, RhoA, and non-muscle myosin II are assembled at the cleavage furrow as a functional unit, which is anchored to the central spindle via MyoGEF-MICSP interaction. To test this hypothesis, we will use a combination of biochemistry, cell biology, and molecular biology, with mammalian cells as a model, to:
- Elucidate the interaction between MyoGEF and non-muscle myosin II
- Elucidate the interaction between MyoGEF and MICSP
- Determine the importance of MyoGEF in the regulation of cytokinesis
- Define the structural basis for MICSP to concentrate at the central spindle.