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Inhibition of Complex Glycosylation Increases the Formation of PrP sc
Author(s) -
Winklhofer Konstanze F.,
Heller Ulrich,
Reintjes Anja,
Tatzelt Jörg
Publication year - 2003
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2003.00088.x
Subject(s) - geldanamycin , endoplasmic reticulum , biology , glycosylation , glycoprotein , microbiology and biotechnology , mannose , hsp90 , membrane glycoproteins , glycan , biochemistry , heat shock protein , gene
N‐linked glycans with complex structure have a major role in the biological activity of a wide variety of cell surface and secreted glycoproteins. Here, we show that geldanamycin, an inhibitor of Hsp90, interferes with the formation of complex glycosylated mammalian prion protein (PrP C ). Similarly to inhibitors of α‐mannosidases, geldanamycin stabilized a high mannose PrP C glycoform and prevented the subsequent processing into complex structures. Moreover, a PrP/Grp94 complex could be isolated from geldanamycin‐treated cells, suggesting that Grp94 might play a role in the processing of PrP C in the endoplasmic reticulum. Inhibition of complex glycosylation did not interfere with the glycosylphosphatidylinositol (GPI) anchor attachment and cellular trafficking of high mannose PrP C to the outer leaflet of the plasma membrane. In scrapie‐infected neuroblastoma cells, however, high mannose PrP C glycoforms were preferred substrates for the formation of PrP‐scrapie (PrP Sc ). Our study reveals that complex glycosylation is dispensable for the cellular trafficking of PrP C , but modulates the formation of PrP Sc .