Role of Pactolus in the innate immune response

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DESCRIPTION (provided by applicant): The mechanism of cell adhesion takes on special significance in studies of the immune response due to the unique nature of the primary constituents of the response, circulating cells. Most organ systems are comprised of cells whose position within that tissue is fixed during differentiation. Alternatively, the immune organ system consists of cells types that are continually being derived de novo from bone marrow precursors and must seek out selected sites within the body for their specific functions. We have isolated a novel gene, dubbed Pactolus that is related to the family of B integrins. This gene was first isolated due to its selective expression in maturing connective tissue mast cells compared to mucosal mast cells. Subsequently we have found that the major cell of the animal that produces Pactolus is the maturing and mature neutrophil. The Pactolus protein is found in two primary configurations: truncated and membrane bound. Upon neutrophil activation, the truncated form is secreted into the supernatant. Additionally, the cell surface expression of the protein is also increased after activation due to the mobilization of intracellular stores. This protein, which by structural analogy must be an adhesion receptor, thus has the potential to bind directly to its ligand with either a cell bound or soluble form. This application proposes to define the function of the Pactolus protein within the cell and the animal by developing a series of approaches to study the cell biology of Pactolus, to analyze its function via the analysis of already created Pactolus knockout animals, and to further our understanding of the transcriptional control of the gene. Understanding its transcriptional control is especially intriguing since production of the protein in inappropriate cells (lymphocytes, etc) leads to cell death. By following the detailed experimental plan of this application, the role of this very interesting and surprising protein in the immune response of the animal will be elucidated