Analysis of Bves function in vesicular transport and cell morphology

Abstract

Bves is a transmembrane protein that influences cell migration, motility, and epithelial integrity through previously undefined mechanisms. In this dissertation, I present evidence that identifies the molecular basis for Bves function. Bves interacts with VAMP3, a SNARE protein that facilitates vesicular transport and specifically recycles β-1 integrin. Here, we demonstrate that Bves is important for VAMP3-mediated receptor recycling that underlies cell adhesion and migration both in vitro and in vivo. Thus, Bves plays a regulatory role in governing SNARE protein function. Similarly, Bves interacts with GEFT, a guanine nucleotide exchange factor that modulates Rho GTPase activity in a broad range of cellular processes including cell migration and protrusion formation. As detailed in this work, Bves regulates cell motility and morphology through regulation of Rho GTPases Rac1 and Cdc42. Thus, through interaction with GEFT, Bves influences Rho GTPase signaling cascades. Taken together, these studies explain the previously reported phenotypes upon Bves depletion at the molecular level and provide a basis to further examine the function of Bves in normal and possibly diseased states. Thus, the significance of this work lies in the identification and characterization of the molecular mechanism underlying Bves function. Overall, this dissertation summarizes our current understanding of Bves function at the molecular level in regulating diverse signal cascades.