Characterization of a novel Vps4 regulator

University Of Utah, Salt Lake City UT

Investigators

Abstract

DESCRIPTION (provided by applicant): Sorting proteins into endosomal compartments is a critical step in coordinating traffic between the plasma membrane, the Golgi apparatus, and the lysosome. It is well known that an array of cargo converges at multivesicular bodies (MVBs), and that a series of protein complexes function in sorting, but how this process is regulated is not well understood. The AAA-ATPase Vps4 has been shown to be a central component of the sorting machinery, required at a late step in cargo sorting and MVB formation. Vps4 has been found to interact with a previously uncharacterized endosomally localized protein. The aims of this proposal will address the following: (1) The localization of this protein will be defined in the context of both wild-type and mutant Vps4. (2) Biochemical characterization, alongside genetic analysis, will be done to determine the molecular composition of the putative complex in which this protein resides. (3) Finally, the role of Vps4 as an ATPase will be assessed to determine how this protein affects Vps4 function. Such experiments will lead to an understanding of how Vps4 regulation plays a role in the MVB path and will contribute to learning more about how disruption of this pathway results in pathogenic states like cancerous cell growth.