Graduation Date

Fall 12-18-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Biochemistry & Molecular Biology

First Advisor

Steve Caplan

Abstract

Membrane trafficking is a basic cell biological process that controls the distribution of proteins and lipids. Our lab is particularly interested in delineating the cellular functions as well as the molecular mechanisms that regulate the C-terminal Eps15 Homology Domain (EHD) protein family of adenosine-5’-triphosphatases in mammalian cells. EHD1-4 are ubiquitously expressed in mammalian tissues and serve partially overlapping but also distinct functions in regulating membrane shaping and fission along the endocytic pathway. Specifically, EHD1 is recruited to tubular recycling endosomes (TREs) by Molecule Interacting with CasL Like-1 (MICAL-L1) and facilitates TRE fission and release of cargo from the perinuclear endocytic recycling compartment (ERC). Recent studies from our lab have shown that the interaction between EHD1 and MICAL-L1 is crucial for TRE biogenesis, dynamics, and the efficient recycling of transferrin, major histocompatibility complex (MHC) class I, and Integrin receptors. However, the roles of EHD1 and MICAL-L1 in cellular processes are less clear. Herein, I describe novel roles for EHD1 and MICAL-L1 in modulating cell signaling through regulating the localization of the non-receptor tyrosine kinase c-Src. In addition, I demonstrate rather unexpected roles for MICAL-L1 and EHD1 in modulating the microtubule cytoskeleton during mitosis.

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