Cell division is a fundamental process for virtually all living systems. The generation of two identical daughter cells requires not only that each cell receives an equal complement of genetic material (DNA) but also that the other contents of the cell be divided equally. The process of physically separating the two daughter cells is known as cytokinesis, and this process involves a contractile ring that physically constricts the cell and splits it in two. Cytokinesis utilizes many of the same mechanisms that are used to regulate cell shape change during migration. Cell shape is dependent on a dynamic structure (the cytoskeleton) that is comprised primarily of the protein actin, and whose behavior is regulated by a number of small signaling molecules. Several conflicting models have been proposed to explain how these small molecules interact to control the cytoskeleton, but the explanatory power of these models has not been clearly established. This project will investigate the regulation of the cytoskeleton by these small signaling molecules and help to clarify the mechanisms by which they function.This research will provide training and educational opportunities for undergraduate and graduate students, with a concerted effort to recruit underrepresented minorities including Native American Indian and Hispanic students. Outreach into high schools will also be performed with the intent to generate in students a long-term interest in science.
In this project, a toolbox of molecular and pharmacological reagents will be combined with biophysical measurements and high-resolution light and electron microscopy to examine how the G proteins Rho, Rac, and Cdc42 coordinate cytokinesis-related shape change in large embryonic cells. Aims 1 and 2 will use a combination of live cell imaging and biophysical analyses to determine what elements of Rac and Cdc42 signaling antagonize Rho-dependent cytokinesis. Aim 3 will take advantage of a unique preparation of the contractile ring to both define its 3D structure and determine how the different elements of Rho signaling contribute to its assembly and function. The results of these studies will advance knowledge in the field of animal cell division research by extending our understanding of the precise 3D architecture of actin and myosin II in the contractile ring that drives cytokinesis.
