This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.
Date of Award
Doctor of Philosophy (PhD)
Membrane trafficking ensures communication among subcellular compartments that are fundamental for eukaryotic life. I examined the major roles of the novel Drosophila gene ema (endosomal maturation defective) in endosomal maturation and autophagy of the degradative membrane traffic. During endocytic trafficking, endosomes undergo a series of maturation processes that involve highly regulated transition of their molecular composition. I found that ema encodes a novel membrane protein that localizes to endosomes in the Drosophila garland cells. Endosomes are aberrantly enlarged in ema mutants as they fail to progress into mature degradative compartments. Through genetic and biochemical approaches, I have shown that Ema interacts with Vps16A, a core component of the class C Vps-HOPS complex to promote endosomal maturation. As cellular membranes are a functional and often physical continuum, the roles of ema expand beyond the endocytic pathway. Autophagy is a self-digestion process that involves engulfment of cytosolic components in double membrane autophagosomes. While defective endosomal maturation would lead to the accumulation of immature autophagosomes, autophagosomes cannot grow but still mature in the ema mutant fat cell. Ema localizes to the Golgi complex and autophagosomes in fat cell. Notably, Ema is required for the autophagy-induced recruitment of Golgi elements to autophagosomes. Therefore, Ema promotes the membrane traffic from the Golgi complex to autophagosome for autophagosomal growth. In conclusion, this study presents the seminal characterization of the versatile novel Drosophila gene ema and provides key insights on the biology of membrane trafficking.
Chair and Committee
J. David Dickman
Dora Angelaki, Paul Gray
Kim, Sungsu, "The role of the novel Drosophila gene Ema for endosomal maturation and autophagy" (2010). Arts & Sciences Electronic Theses and Dissertations. 507.
Available for download on Monday, December 15, 2110