T BRUCEI NUCLEOLAR PROTEIN: MECHANISM OF LOCALIZATION

Seattle Biomedical Research Institute, Seattle WA

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Abstract

DESCRIPTION (Adapted from the Applicant's Abstract): The parasitic protozoan Trypanosoma brucei is the causative agent of African sleeping sickness from which approximately 50 million people in Africa are at risk. T. brucei is an important model organism for the study of kinetoplastid cell biology. The T. brucei phosphoprotein Nopp44/46 is localized to the nucleolus, an organelle housing ribosome biogenesis. The function of Nopp44/46 is currently unclear, however, its abundance and its ability to bind both proteins and nucleic acids hint that it works as a scaffold within the nucleolus. Nopp44/46 does not contain an identifiable nuclear localization signal (NLS) and there is no known consensus nucleolar targeting sequence, leaving us with the question as to how the protein enters the nucleus and accumulates in the nucleolus. One goal of this proposal is to define the regions of Nopp44/46 responsible for its nuclear and nucleolar localization. Additionally, Nopp44/46 interacts with a novel nucleolar G-protein, THNOGI. Although the role of THNOGI in Nopp44/46 localization or function has not been determined, we hypothesize that Nopp44/46 hitchhikes into the nucleus by interacting with THNOGI. The objective of this proposal is to further characterize the mechanism of both nuclear and nucleolar localization of Nopp44/46 and define the role of THNOGI in this localization. The results of the proposed work will expand the knowledge of localization mechanisms and may also provide clues as to specific functions of THNOGI.