A protein sharing homology with anti-coaggulants known to competitively inhibit integrin receptor binding to fibrinogen has been described in a protist, Dictyostelium discoideum. This protein, AmpA, functions as a novel signaling molecule that plays both autocrine and paracrine roles controlling cell adhesion and cell fate specification during growth and development. Dictyostelium is a model system extensively used to study cell migration and development. AmpA functions to reduce cell-cell and cell-substrate adhesion, promoting migration of these cells facilitating their ability to forage for food. During the developmental phase of the life cycle the expression of the ampA gene is restricted to a small, but highly motile subset of cells whose migrations are necessary for proper morphogenesis. AmpA expression is essential for migration of these cells. It also acts as a lateral inhibitory signal that prevents adjacent cells from assuming a prespore fate. The simplest model for AmpA function is that it is a modulator of an integrin like receptor. Integrin receptors, however, have not been identified outside of metazoan organisms and there is no obvious integrin receptor that can be identified by sequence homology in Dictyostelium. The objective of this project is to identify the adhesion receptor that is modulated by interaction with the AmpA protein and to identify additional genes that are candidates to function in the AmpA modulated signaling pathway. Aim 1: will use biochemical and molecular genetic approaches to identify and characterize the receptor to which AmpA binds. Aim 2: will use a genetic approach, isolation of second site suppressor mutations, to identify additional genes that function in the AmpA mediated signal transduction pathways. Using AmpA as a probe to identify the adhesion receptors that are modulated by its action and to identify other genes that function downstream in the AmpA signaling pathway should help to elucidate the nature of cell-substrate adhesion and its modulation to promote cell migration and provide insight to how the metozoan integrin paradigm evolved. It should be noted that this project will involve graduate and undergraduate students, some of whom are members of under represented minorities. The research experience gained working on this project will contribute to their scientific education.
