15. Physiological Functions of the Cellular Prion Protein Principal Investigator: Marco Prado, University of Western Ontario
Co-investigators:
Stephen Ferguson, University of Western Ontario
Collaborators:
Vilma Martins, Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz
Vania Prado, University of Western Ontario
Gerald Zamponi, University of Calgary
Project Description:
The identification of PrPC functions is pivotal for understanding prion diseases. Strong evidence for PrPC physiological functions derives from previous description of its association with the Stress Inducible Protein 1 (STI1). Recently, it has been demonstrated that STI1 is secreted by astrocytes and functions as a neurotrophic factor upon interaction with PrPC. Indeed, in order to characterize possible PrPC loss-of-function mechanisms it is crucial to define pathways involved with STI1 secretion, PrPC transduction of cellular signals and it is necessary to disturb STI1-PrPC interaction in vivo. This project aims to: 1 - determine the role post-translational modifications such as ubiquitylation and SUMOylation for STI1 secretion; 2 - evaluate the ability of PrPC to interact with a transmembrane protein, LRP1, and the participation of clathrin-mediated endocytosis to evoke PrPC-STI1 cellular signaling; and, 3 - generate STI1 deficient mice to characterize the physiological consequences of STI1-PrPC engagement in vivo.
(Recruitment 2008)
Last Updated: 5/3/2010 5:18:12 PM
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