Regulation of the Cytoskeleton by Signaling Proteins during Quorum Sensing

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The ability of mammalian cells to sense the density of the cells around them (quorum sensing) plays an important role in such fundamental processes as embryogenesis, proliferation and differentiation, and cell migration. Without quorum sensing a developing embryo would be unable to properly proportion its cells into different tissue types. Such control requires integrating secreted factors, signal transduction molecules, and cellular machinery. In mammals, the sheer number of players involved in these processes creates an unwieldy morass of interconnected proteins, making it difficult to study. This project is designed to untangle this snarl by using the social ameoba, Dictyostelium discoideum, as a model. Dictyostelium cells display many of the characteristics of mammalian cells, including, but not limited to, motility, differentiation, development and cell to cell signaling. Thus, this protist is an excellent model for mammalian cell behavior, especially quorum sensing. When starved, Dictyostelium cells will undergo a period of differentiation and development leading to the formation of a multicellular organism. However, this process will not begin unless there are sufficient numbers of starving cells to form a full sized organism. Therefore, these cells are able to sense the density of the starving cells around them and respond appropriately. This project will delineate how three signal transduction molecules (phospholipase Dbeta and the protein kinases TklA and PakD) work together to control changes in the actin cytoskeleton and the decision to develop. By uncovering the function of these proteins in Dictyostelium discoideum, a better understanding of their roles in quorum sensing in mammalian cells can be gained, and with it, a better understanding of their roles in development.Broader Impact:This project advances discovery while promoting participation of underrepresented groups in the learning process, as Hunter College is a minority serving institution with a 60% female student body. Underrepresented students and one postdoctoral researcher will be actively engaged in designing, interpreting and presenting experiments. As part of this project, two lab modules designed to teach genetic analysis to Biology, Biochemistry and Neuroscience majors will be created, implemented and assessed. The postdoctoral researcher will help design the modules, train the lab instructors and teach students, enabling him to acquire skills in course creation, coordination and lecturing. These lab modules will be disseminated on-line to the broader teaching community (www.dictybase.org), extending the reach to those historically underrepresented in the sciences.