Paralog-Specific Functions of Rab27a and Rab27b in Exosome Secretion

Extracellular vesicles (EVs) are membrane-bound compartments that are exported out of cells. There are two major subpopulations of EVs: microvesicles and exosomes. Exosomes have garnered particular interest in the scientific community due to recent studies suggesting a role for exosomes in intercellular communication in both normal and disease states. Additionally, exosomes can be utilized as diagnostic biomarkers for a variety of disease conditions. Despite broad interest in exosomes, little is known about how their release is regulated. Rab27a and Rab27b are two very closely related proteins that regulate different steps of exosome secretion. How such similar proteins can control separate steps of this pathway is not well understood. My proposed research aims to characterize the distinct mechanisms by which Rab27a and Rab27b control exosome secretion using both genetic and biochemical approaches. Obtaining a more comprehensive understanding of how Rab27a and Rab27b regulate exosome secretion will provide insight into how exosomes […]

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Role of Bin-Amphiphysin-Rvs Proteins in Clathrin-Mediated Endocytosis

Our project goal is to better understand the role of BAR (Bin-amphiphysin-Rvs) proteins in clathrin-mediated endocytosis (CME) and study their interaction with endocytic branched actin networks, using the budding yeast Saccharomyces cerevisiae as a model organism. Most endocytic BAR proteins contain an N-terminal banana-shaped BAR domain that preferentially binds curved membranes and a C-terminal SRC-homology 3 (SH3) domain that interacts with numerous components of the endocytic machinery. BAR proteins are thought to stabilize and scaffold curved membranes as well as facilitate vesicle scission, but exact mechanisms of these functions remain unclear. Specifically, we aim to understand how the BAR protein complex Rvs161/167 facilitates vesicle scission, learn more about how this complexs SH3 domain influences endocytic actin dynamics, and see if this phenomenon is conserved among other similarly-structured endocytic BAR proteins, like the branched actin nucleator Bzz1.

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