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Our research focuses on the return of internalized macromolecules to the cell surface from endosomes (endocytic recycling), a basic cell biological process that is of fundamental importance to many areas of biomedicine. For instance, endocytic recycling is a key control point in the insulin-stimulated movement of glucose transporters (Glut4) from endosomes to the plasma membrane, a process that goes awry in type II diabetes. A better understanding of how endocytic recycling functions will be profoundly important in identifying therapeutic targets to combat this and other diseases.
For many of these studies we focused on a system that we pioneered, the C. elegans intestine, a very simple model that allows facile analysis of endocytic membrane transport pathways within intact polarized epithelia.
The proposed experiments will provide significant new insights into how endocytic recycling works. Given the high level of phylogenetic conservation of such pathways from worms to mammals, and our parallel analysis in human cells, we expect that our work will provide extensive insight into key conserved elements relevant across species. This work is important for understanding disease etiology and in identifying therapeutic targets for disease intervention.
The current project focuses on a conserved transmembrane protein called MIG-14/Wntless. This protein is important for signaling and trafficking in the WNT pathway. The Aresty student will work with a current postdocin the lab to study the mechanisms used to recycle this protein to the Golgi after its endocytosis from the plasma membrane.
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