|Institution:||University of Cincinnati|
|Department:||Medicine: Developmental Biology|
|Keywords:||Biology; Retromer; apical-basal polarity; Crumbs; Toll pathway; vps35; Drosophila|
|Full text PDF:||http://rave.ohiolink.edu/etdc/view?acc_num=ucin1331296365|
The retromer complex is a membrane anchored intracellular protein complex.Retromer recognizes specific transmembrane cargos and mediates their transportationfrom endosomes to trans-Golgi network (TGN). Vacuolar protein sorting-associatedprotein 35 (Vps35) is a major component of retromer. Through analyzing phenotypes ofDrosophila vps35 (dvps35) mutants/RNAi, our lab previously identified a role ofretromer in mediating WNT secretion. However, dvps35 mutants/RNAi displayedadditional developmental defects which were not relevant to WNT secretion. Thisindicated additional roles of retromer during Drosophila development. My workpresented here uncovered two additional roles of retromer in (1) regulating apical-basalpolarity in epithelial cells; (2) suppressing auto-activation of the Drosophila immunesystem. Further analysis showed that retromer regulated apical-basal polarity throughrecycling Crumbs, which acted as a novel retromer cargo. I also found that retromersuppressed auto-activation of the immune system by regulating Spatzle, the ligand in theToll signaling pathway. In summary, this dissertation work expanded our understandingof the transmembrane cargos and the biological functions of retromer.