Wnts are secreted signaling proteins that control multiple developmental processes and have been implicated in several human cancers. All Wnt proteins, including Wingless, a Drosophila member of the Wnt family, associate with cell membranes. This membrane-association is a result of posttranslational acylation and strong affinity for heparin sulfate proteoglycans. Despite its association with cell membranes, Wingless acts over several cell diameters in a number of developmental contexts. It has been suggested that transport is achieved by liprotein particles but functional evidence is incomplete and nothing is known on how Wg is packaged into such particles. During my postdoctoral research I will study the secretion and release of Wingless by expressing cells. Specifically, I will define the pathway of Wingless secretion and its site of export from the cell. Second, I will identify novel proteins required for the secretion and release of functional Wingless protein. This will could uncover specialized secretory pathway and will provide a framework to understand how Wingless functions with tissues. Understanding the pathways that regulate short and long range signaling by Wnts is likely to have an impact both in basic sciences (e.g. about the cell biology of lipid modified secreted proteins) and in medicine (providing potential targets for drug that would modulate this important signaling pathway).
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