Cellular prion proteins in human platelets show a phenotype different to those in brain tissues

Abstract

Prion diseases are characterized by high accumulation of infectious prion proteins (PrP(Sc)) in brains. PrP(Sc) are propagated by the conversion of host-encoded cellular prion proteins (PrP(C)) which are essential for developing the disease but are heterogeneously expressed in brains. The disease can be transmitted to humans and animals through blood and blood products, however, little attention has been given to molecular characterization of PrP(C) in blood cells. In this presented study, we characterized phenotypically PrP(C) of platelets (plt) and characterized the proteins regarding their glycobanding profiles by quantitative immunoblotting using a panel of monoclonal antibodies. The glycosylation patterns of plt and brain PrP(C) were compared using the ratios of di-, mono-, and non-glycosylated prions. The detergent solubility of plt and brain PrP(C) was also analyzed. The distinct banding patterns and detergent solubility of plt PrP(C) differed clearly from the glycosylation profiles and solubility characteristics of brain PrP(C). Plt PrP(C) exhibited single or only few prion protein types, whereas brain PrP(C) showed more extensive banding patterns and lower detergent solubility. Plt PrP(C) are post-translational modified differently from PrP(C) in brain. These findings suggest other or less physiological functions of plt PrP(C) than in brain.

Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

“…Similar to neutrophils from LPS-treated mice (Fig. 1F), as well as human platelets (27), immunoblots of DEX-treated bone marrow cells included predominantly protein species with molecular masses higher than those of brain tissue. Notwithstanding, deglycosylation of protein extracts reduced the immunodetected protein to a single band of ϳ25 kDa (Fig.…”

“…Membranes were stripped and reprobed for Erk2 as a loading control. Protein deglycosylation with N-glycosidase F was done as per manufacturer's protocol, except that the enzyme incubation time was increased from 3 to 16 h, as described (27).…”

Effects of metal binding on solubility and resistance of physiological prions depend on tissues and glycotypes

“…Physiological prion proteins (PrP C ) are composed of highly heterogeneous isoforms in different tissues and brain areas [Beringue et al, 2003;Kuczius et al, 2009], and human brain PrP C clearly differs from human platelet PrP C in expression and banding patterns [Kuczius et al, 2011a]. Furthermore, PrP C proteins are able to interact with metal ions, in particular with copper and zinc [Jobling et al, 2001].…”

“…PrP C of platelets and of brains which both are embedded in protein complexes are composed of several subtypes which are dissoluble differentially with various detergents and which demonstrate distinct glycoprotein profiles [Kuczius et al, ]. Irrespective from different glycosylation grades distinct PrP C types were highly soluble in detergent solutions while others were low soluble and were detected in the pellet fractions.…”

“…Metal binding is associated with structural transformations in PrP. However, different phenotypes of PrP C are present in platelets and brains [Kuczius et al, ]. Platelet PrP C has an increased solubility in detergents and consists of higher amounts of glycosylated PrP C than brain PrP C .…”