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Date of Award

Winter 12-15-2010

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

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.

Language

English (en)

Chair and Committee

J. David Dickman

Committee Members

Dora Angelaki, Paul Gray

Comments

Permanent URL: https://doi.org/10.7936/K7KW5D7G

Available for download on Monday, December 15, 2110

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