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Molecular Mechanisms of the Membrane Sculpting ESCRT Pathway
- Remec Pavlin, Mark
- Advisor(s): Hurley, James H
Abstract
The Endosomal Sorting Complex Required for Transport (ESCRT) is an ancient, complex machinery that remodels and scissions cellular membranes. Uniquely, the ESCRTs remodel and scission membranes in a reverse topology – away from the cytosol. Since their discovery the ESCRTs have been identified in a large number of cellular processes, but detailed mechanistic understanding has proven difficult. As a system of over 20 components that rapidly and dynamically rearrange themselves to constrict and scission membranes, the ESCRTs prove a difficult machinery that will require high-quality reconstitutions to study.
In Chapter 1 I provide an introduction to the ESCRTs and describe recent advances toward achieving a consensus on the mechanism of ESCRT-mediated membrane remodeling and scission. In Chapter 2 I discuss the first reconstitution of ESCRT-mediated membrane scission, combining microscopy, microfluidics, and optical trapping to achieve this goal. In Chapter 3 I describe a novel function of the ESCRTs, finding that CHMP1B, IST1, and Spastin are capable of normal-topology membrane scission. Finally, in Chapter 4 I provide an outlook on the remaining challenges in the field, and the approaches that will be crucial for tackling them.
Main Content
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