Scrapie prions selectively modify the stress response in neuroblastoma cells.
The fundamental event underlying scrapie infection seems to be a conformational change in the prion protein. To investigate proteins that might feature in the conversion of the cellular prion protein (PrPC) into the scrapie isoform (PrPSc), we examined mouse neuroblastoma N2a cells for the expression and cellular distribution of heat shock proteins (Hsps), some of which function as molecular chaperones. In scrapie-infected N2a (ScN2a) cells, Hsp72 and Hsp28 were not induced by heat shock, sodium arsenite, or an amino acid analog, in contrast to uninfected control N2a cells, while other inducible Hsps were increased by these treatments. Following heat shock of the N2a cells, constitutively expressed Hsp73 was translocated from the cytoplasm into the nucleus and nucleolus. In contrast, the distribution of Hsp73 in ScN2a cells was not altered by heat shock; the discrete cytoplasmic structures containing Hsp73 were largely resistant to detergent extraction. These alterations in the expression and subcellular translocation of specific Hsps in ScN2a cells may reflect the cellular response to the accumulation of PrPSc. Whether any of these Hsps feature in the conversion of PrPC into PrPSc or the pathogenesis of prion diseases remains to be established.
Tatzelt
J
J
Department of Neurology, University of California, San Francisco 94143, USA.
Zuo
J
J
Voellmy
R
R
Scott
M
M
Hartl
U
U
Prusiner
S B
SB
Welch
W J
WJ
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D009447:Neuroblastoma; D011328:Prions / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D012608:Scrapie / Q000821:virology*; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D011328:Prions; D014157:Transcription Factors