All eukaryotic cells share the ability to heal themselves and to divide; these capacities are essential for life and, when deficient, result in a variety of human diseases. While both processes occur in response to very different stimuli?damage in the case of healing, anaphase onset in the case of cell division?the same core players are employed: Rho GTPases and their ultimate targets, the components of the actomyosin cytoskeleton. In keeping with the fact that the stimuli are different, the regulators that control Rho GTPases in cell repair and cell division differ considerably. However, we have discovered that in both cell repair and cell division, the regulators impact the Rho GTPases in a fashion that produces GTPase activity waves. For cell repair, two complementary, concentric waves, one of Cdc42 activity and one of Rho activity, form around wounds and close inward, with an ring of actomyosin closing over the wound in their wake. For cytokinesis, randomly moving waves of Rho activity are initially found throughout the cell cortex, but become focused at the cell equator by the mitotic spindle. Once confined to the equator, the waves direct the assembly of the actomyosin-based cytokinetic apparatus, which follows the waves inward and pinches the cell in half. Here we propose experiments designed to determine how the waves arise, how they assume their characteristic forms, and how they are interpreted by the cell cortex to build the actomyosin-based structures needed for healing and cell division. The proposed work will provide fundamental new insights into cell repair and cell division. Given the medical importance of these processes, the proposed work will likewise benefit efforts to improve human health.
Cells in our body are constantly being damaged and constantly fixing themselves. However, when cells lose the ability to repair themselves, diseases occur. Similar, cells in our body are constantly dividing, but when cell division fails, diseases result. The proposed work will let us understand how cells repair themselves and how they divide, which will permit us to better treat those diseases.
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