Characterization of the prion protein in human urine.
The presence of the prion protein (PrP) in normal human urine is controversial and currently inconclusive. This issue has taken a special relevance because prion infectivity has been demonstrated in urine of animals carrying experimental or naturally occurring prion diseases, but the actual presence and tissue origin of the infectious prion have not been determined. We used immunoprecipitation, one- and two-dimensional electrophoresis, and mass spectrometry to prove definitely the presence of PrP in human urine and its post-translational modifications. We show that urinary PrP (uPrP) is truncated mainly at residue 112 but also at other residues up to 122. This truncation makes uPrP undetectable with some commonly used antibodies to PrP. uPrP is glycosylated and carries an anchor which, at variance with that of cellular PrP, lacks the inositol-associated phospholipid moiety, indicating that uPrP is probably shed from the cell surface. The detailed characterization of uPrP reported here definitely proves the presence of PrP in human urine and will help determine the origin of prion infectivity in urine.
Dagdanova
Ayuna
A
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Ilchenko
Serguei
S
Notari
Silvio
S
Yang
Qiwei
Q
Obrenovich
Mark E
ME
Hatcher
Kristen
K
McAnulty
Peter
P
Huang
Lequn
L
Zou
Wenquan
W
Kong
Qingzhong
Q
Gambetti
Pierluigi
P
Chen
Shu G
SG
D006801:Humans; D017096:Prion Diseases / Q000652:urine*; D011328:Prions / Q000472:pathogenicity / Q000652:urine*; D011499:Protein Processing, Post-Translational
D011328:Prions