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Cytokinesis: Biochemically controlled mechanics Cell division is essential for growth and replenishment of tissues and organs and to achieve this renewal, the human body has nearly a billion cell division events underway at every moment in time. A number of developmental programs are also tightly coupled to cell division, including tissue morphogenesis and stem cell maintenance. However, no cellular process is 100% efficient, and cell division failure is deleterious, leading to tumorigenesis. Therefore, cell division research has significant implications for understanding normal physiology and disease. |
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| In our studies, we use Dictyostelium discoideum as a model for cytokinesis. This simple protozoan performs cytokinesis and cell motility in a manner similar to human cells yet it is tractable for genetic, molecular, biochemical, and biophysical methods. We take advantage of each of these experimental approaches to discover new factors involved in cytokinesis and to learn how they contribute to the process. We have also developed a number of quantitative assays for studying the physical aspects of cell division and cell function. By combining these approaches, we have demonstrated that myosin-II increases the active, dynamic nature of the living cortex while actin crosslinking proteins control its mechanical resistance. The balance between dynamic rearrangements and resistance determines how cells change shape during cytokinesis. |
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| Recently, we discovered a novel mechanosensory system that allows dividing cells to sense shape perturbations so that the cells can correct the disturbance and complete cytokinesis normally. By studying this system, we are identifying the molecular basis of mechanosensation and mechanotransduction during cell division. Mechanosensing is fundamental to a wide variety of cellular processes critical to healthy and pathological states. Tumor cells can grow in the absence of surface attachment, a feature that classically defines cellular transformation, indicating that changes in mechanotransduction are an important part of cancer progression. Bone remodeling, blood pressure regulation, and hearing are all examples of normal processes that depend on mechanosensing. Yet, the cellular and molecular mechanisms of mechanosensing are not well understood in any system. Using a combination of molecular genetic and micromechanical approaches, we are discerning the contributions from molecular motors, microtubule network, actin-associated proteins, signaling proteins, and stretch receptors to mechanosensing. | |
