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Document Type:Latin Dissertation
Language of Document:English
Record Number:52401
Doc. No:TL22355
Call number:‭MR48095‬
Main Entry:David Tse-Shen Lin
Title & Author:Prion protein topologies and the effect on its neuroprotective functionDavid Tse-Shen Lin
College:McGill University (Canada)
Date:2008
Degree:M.Sc.
student score:2008
Page No:120
Abstract:The normal prion protein (PrP) is ubiquitously expressed and is especially abundant in the brain. However, the major physiological function of PrP has remained elusive. Recently, it was demonstrated that PrP prevents Bcl-2 associated protein X (Bax)-mediated cell death by inhibiting the initial Bax conformational change that converts cytosolic Bax into a pro-apoptotic protein (Roucou et al., 2005). To further determine the form and subcellular location of PrP with anti-Bax function, we co-expressed various Syrian hamster PrP (SHaPrP) mutants that favor specific PrP topologies and subcellular localization with N-terminally green fluorescent protein tagged pro-apoptotic Bax (EGFP-Bax) in MCF-7 cells and primary human neurons. The PrP mutants that synthesize transmembrane PrP lose their anti-Bax function, whereas those that exclusively synthesize secreted or cytosolic PrP (CyPrP) retain protection comparable to that of wild type PrP in both cell types. Furthermore, co-expression of CyPrP with these mutants rescues the anti-Bax function. Addition of extracellular PrP supports only minimally the anti-Bax function. Therefore, the results indicate that the CyPrP is the predominant form of PrP with anti-Bax function. We have previously excluded the need for other Bcl-2 family members in the antiBax function of PrP. Here, we also fail to co-immunoprecipitate PrP and Bax indicating that PrP's anti-Bax function is not through a direct PrP-Bax interaction in the cytosol. We conclude that there must exist a cytosolic Bax interactor through which PrP exerts its effect.
Subject:Biological sciences; Neurosciences; 0317:Neurosciences
Added Entry:McGill University (Canada)