The division of one cell to form two cells, or cytokinesis, is fundamental to the development of all known multi-cellular organisms, as well as the propagation of life between generations. The intracellular mechanisms that mediate the physical deformation of the cell membrane during division have proven to be remarkably robust, with multiple processes functioning together to achieve bisection. Here, I present my doctoral work, which seeks to illuminate the dynamic molecular interplay that coordinates and drives cytokinesis in the Caenorhabditis elegans single-cell zygote. In Chapter 1, I begin with an introduction on cytokinesis and the many proteins known to regulate cell division. Chapter 2 presents a detailed review of three intracellular signaling molecules that mediate the spatial control of cytokinesis, known as Rho family small GTPases. In Chapter 3, I present work in which we inactivated specific cytokinesis protein functions at precise stages of the division process, in order to map out the first “temporal atlas” of essential cytokinetic functions. In Chapter 4, I present evidence that the GTPase CDC-42 and the cortical polarity machinery sequester cytokinesis-inhibiting proteins away from the division plane and protect the fidelity of cytokinesis. Chapter 5 lays out preliminary evidence that another GTPase, RAC-1, is a suppresser of cytokinesis and must be inactivated in the division plane specifically by a spindle-associated regulatory protein. Through this body of work, I have attempted to elucidate the underpinnings of the complex intracellular orchestra that drives cytokinesis. This work provides valuable insight, not only into how this vital process occurs, but also how the disruption of its components could lead to the development of complex diseases like cancer.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/D8P849ZS |
| Date | January 2015 |
| Creators | Jordan, Shawn |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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