NR AWMZ
AU Saghafi,S.; Spilman,P.R.; DeArmond,S.J.; Prusiner,S.B.; Lingappa,V.R.
TI Regulation of PrPc topology is developmentally dependent
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-44
PT Konferenz-Poster
AB We previously reported that temporal dysregulation of PrPc expression in inducible transgenic mice leads to upregulation of transmembrane CtmPrP and severe neurodegeneration. Further analysis suggested that the upregulation of CtmPrP may be developmentally dependant. We now extend our previous findings and observe a close developmental correlation between the time point of PrP induction, the degree to which CtmPrP is upregulated, and the level of cell death observed. Our data identifies the developmental window between birth and postnatal day 3 to be crucial for transmediated changes that lead to the dramatic induction of CtmPrP and concomitant neurodegeneration. Furthermore, our data substantiates previous finding that CtmPrP is a trigger of cell death by a caspase 3-mediated apoptotic pathway. Most importantly, our data prove that wild-type PrPc has the intrinsic capacity to be expressed as either CtmPrP or SecPrP, which as we have previously shown have distinct functional roles as pro- and anti-apoptotic mediators of cellular survival, respectively. This model system may prove valuable to identify crucial trans-acting factors that may also participate in the aetiology of infectious or sporadic prion disease forms that are suggested to be trans mediated.
AD S. Saghafi, V.R. Lingappa: Institute for Neurodegenerative Diseases, Department of Physiology, University of California, San Francisco, USA; P.R. Spilman, S.J. DeArmond: Institute for Neurodegenerative Diseases, Department of Pathology, University of California, San Francisco, USA; S.B. Prusiner: Institute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, USA. E-mail: sam.saghafi@ucsf.edu
SP englisch
PO Italien