(from abstract) The ability of eukaryotic cells to move over their substrate is important for such processes as embryonic development, wound healing and cancer metastasis. The mechanism is not known; however, it is clear that the action cytoskeleton plays a central role. One important aspect of cell movement is protrusion of the leading edge, which is dependent on actin polymerization. The overall aim of this application is to understand at a molecular level how polymerization of actin is regulated, and how it generates force for movement. Much of the work will be on the mechanism of the movement of a pathogenic bacterium, Listeria, which uses host cell actin polymerization to move through the cytoplasm and spread from cell to cell. The investigators propose to use biochemical fractionation to determine how Listeria induces polymerization of an actin tail. They also propose to determine the structure of the Listeria actin tail and how filaments in the tail depolymerize. They then intend to use what they learn in Listeria and apply it to understanding the movement of whole cells. One focus will be the mechanism by which the filopodia of neuronal growth cones extend and retract.
| Irimia, Daniel; Charras, Guillaume; Agrawal, Nitin et al. (2007) Polar stimulation and constrained cell migration in microfluidic channels. Lab Chip 7:1783-90 |
| Charras, Guillaume T; Yarrow, Justin C; Horton, Mike A et al. (2005) Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435:365-9 |
| Cramer, L; Mitchison, T J (1993) Moving and stationary actin filaments are involved in spreading of postmitotic PtK2 cells. J Cell Biol 122:833-43 |
