Signaling Specificity of Drosophila Serpentine Receptors

DESCRIPTION (provided by applicant): Cellular polarization underlies many critical biological phenomena: in wound healing, cells migrate to the site of lesion; neurons project axons that navigate to distant targets; and in the immune response, cells move to engulf invading pathogens. All these behaviors are mediated by the polarization of the cytoskeleton in response to external cues. A closely related phenomenon is called planar cell polarity (PCP). Here, cells arrayed in epithelia coordinately polarize so that all cells project their cuticular secretions in the same direction. Bird feathers, mammalian hairs and fish scales exemplify this phenomenon. This application is directed to understand how PCP is established. Drosophila is a model experimental organism in which PCP can be effectively investigated. Each cell uses a serpentine receptor called Frizzled (Fz) to decode an external gradient to direct its polarization. Serpentine receptors are typically transduced by trimeric G proteins, and the focus of this application is to understand the roles played by the fly G1o (and other PCP proteins) in Fz transduction and the organization of the cytoskeleton. We will use genetic, molecular and biochemical techniques to determine the exact relationship between Frizzled and G1o, and identify the proteins downstream of G1o in the transduction pathway. These studies will elucidate the mechanisms by which cells decode gradients, polarize their cytoskeletons, and communicate their actions to neighbors. PUBLIC HEALTH RELEVANCE: Polarization of the cytoskeleton within cells is required for many critical bodily processes such as wound healing, formation of nerve connections, and the eradication of infection. A field of cells can coordinately organize their polarizations, as demonstrated by the organization of the cilliary bundles of the inner ear that permit us to hear sound. This application is designed to study planar cell polarity in fruit flies, to understand how cells can polarize and coordinate those polarizations in larger scale structures.