NR AXPV
AU Kimura,T.; Ishikawa,K.; Nishimura,Y.; Schätzl,H.M.; Doh-ura,K.
TI Screening for Endogenous Factors Involved in the Formation of Protease Resistant Prion Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.11
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
It is suggested that endogenous factors are involved in the formation of PrPsc/res or the conformational change from PrPc into PrPsc/res. In order to identify the factors, we used RNAi technique in persistently prion-infected neuroblastoma cells and knocked down genes of the proteins on the cell membrane. Modification in PrPres formation in this study was assayed by immunoblotting, and at the same time, reduction in mRNA expression levels was confirmed by quantitative RT-PCR. So far, more than 200 genes have been screened and the data of protein "G" is shown here as a representative.
The protein "G" is a component of a certain receptor in neuronal cells. PrPres formation levels were reduced in the knockdown experiment with either vector-driven short-hairpin RNAs or synthetic ones targeting each different sequence in the gene. On the other hand, PrPc expression levels were increased. Further, treatment of the cells with a selective antagonist for the receptor composed of "G" exhibited the similar results to the knockdown study, and treatment with a potent agonist for the receptor showed the opposite results to the knockdown study. These findings suggest that the receptor composed of "G" might be involved in the PrPres formation or the PrP conformational change, and could be a new target for anti-prion drugs.
AD T. Kimura, K. Ishikawa, Y. Nishimura, K. Doh-ura, Tohoku University Graduate School of Medicine, Department of Prion Research, Japan; H.M. Schätzl, Technical University of Munich, Institute of Virology, Germany
SP englisch
PO Schottland