"The ability of cells to move invasively through the cellular junctions of the endothelial vasculature underlies the function of the immune system and the metastatic spread of cancer. How the invading and the invaded cells communicate to synchronize their actions during this behavior remains unclear. We are studying these questions using the developmental migration of Drosophila immune cells through an epithelial barrier. We have identified many mutants required for this process in a preliminary screen and are particularly intrigued by 5 transporter genes. These are excellent candidates to be transmitting coordinating signals between the immune cells and the epithelia and will be the focus of this proposal. We seek to determine which of these transporters are specific for invasive migration and could act at the cell surface to facilitate signal transmission; we will pick one which fits this criterion and create a null allele of it. We will then investigate what process this transporter affects. We have shown previously that invasion requires changes in adherens junctions and integrin affinity through the relocalization of an integrin modulator Rap1. We will examine our chosen mutant in these assays, and develop new ones to assess volume changes and chain migration if needed. Then we will determine if the role in junctional penetration that we identify for this gene in Drosophila is also conserved in vertebrate immune cells. Thus our work will identify a new component for invasion, the process it plays a role in and its relevance for important vertebrate physiology."