In phagocytosis, binding of a particle signals a rapid recruitment and polymerization of actin that drives pseudopod extension. Although cell-surface receptors for phagocytosis have been identified in platelet, macrophages, and polymorphonuclear leukocytes, the molecular details of how receptors signal the dynamic changes in the actin-based cytoskeleton are unclear. The long-term goal of this project is to understand how specific localized cytoskeletal responses occur in the phagocytic process. The specific objective of this proposal is to identify cell surface molecules responsible for the recognition and binding step of phagocytosis. A primarily biochemical approach will be used, with the expectation that the knowledge gained will guide a molecular genetic analysis of phagocytosis in Dictyostelium discoideum. The purpose of these studies is to generate a based of knowledge that will support and guide future biochemical and genetic analyses of the interactions between cell surface molecules and the cytoskeleton. %%% Phagocytosis, or "cell eating," is a process whereby cells bind to and subsequently internalize particulate materials. The process is critical to free-living amoebae, who depend on phagocytosis of food particles (e.g., bacteria) for their survival. The process is also critical to mechanisms of animal defense against microbial pathogens, both in invertebrate systems, where phagocytic cells may be the primary mechanism of immunity against such pathogens, and in higher animals, including man where phagocytosis serves a far more complex series of immune functions. Phagocytic processes are also involved in a broad variety of non-immune related cellular "clean- up" functions, such as the clearing of smoke particles in the lungs by macrophages. This project has the potential to increase our understanding of this fundamental life process.
