The expression of prion protein (PrPC) in the megakaryocyte lineage

Starke, Richard; Harrison, Paul; Mackie, Ian; Wang, G; Erusalimsky, Jorge D.; Gale, Rosemary E.; Jm, Massé; Cramer, Elisabeth M.; Pizzey, Arnold; Biggerstaff, John; Machin, Samuel J.

doi:10.1111/j.1538-7836.2005.01343.x

Cited by 29 publications

(23 citation statements)

References 26 publications

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“…The current study localizes PrP C to platelet alpha granule, but not dense granule, membranes, confirming a recent study by Starke et al 9 Thus, PrP C is present with proteins such as the ␣IIb/␤3 integrin, CD62 (P-selectin), CD36, and the GPIb/V/IX complex [32][33][34][35] inherent in the alpha granule membrane, and, in common with these other proteins, there is an activation-mediated increase in expression of PrP C on the external platelet surface. The function of PrP C in platelets is unknown; preincubation with anti-PrP C Abs has a limited effect on platelet adhesion to a variety of matrices but no effect on agonist-induced aggregation (Robertson et al, unpublished); therefore, it is unlikely that PrP C plays a significant role in either of these platelet functions.…”

Section: Discussionsupporting

confidence: 80%

“…7 In the former case the surface expression of PrP C is increased following stimulation, suggesting an additional internal membrane source of the protein, 8 recently shown to be alpha granule membranes. 9 Furthermore, platelet activation is associated with the accumulation of PrP C in releasates, 10 and in platelet concentrates, stored for up to 10 days, there is an increase in initially the microsomal, then plasma levels of PrP C . 11 Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative disorders, including CreutzfeldtJakob disease (CJD), Gerstmann-Straussler-Schienker syndrome, and fatal familial insomnia in humans; scrapie in sheep; and bovine spongiform encephalopathy (BSE) in cattle.…”

Section: Introductionmentioning

confidence: 99%

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Cellular prion protein is released on exosomes from activated platelets

Robertson

Booth

Beniac

et al. 2006

Blood

123

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Cellular prion protein (PrP C ) is a glycophosphatidylinositol (GPI)-anchored protein, of unknown function, found in a number of tissues throughout the body, including several blood components of which platelets constitute the largest reservoir in humans. It is widely believed that a misfolded, protease-resistant form of PrP C , PrP Sc , is responsible for the transmissible spongiform encephalopathy (TSE) group of fatal neurodegenerative diseases. Although the pathogenesis of TSEs is poorly understood, it is known that PrP C must be present in order for the disease to progress; thus, it is important to determine the physiologic function of PrP C . Resolving the location of PrP C in blood will provide valuable clues as to its function. PrP C was previously shown to be on the alpha granule membrane of resting platelets. In the current study platelet activation led to the transient expression of PrP C on the platelet surface and its subsequent release on both microvesicles and exosomes. The presence of PrP C on platelet-derived exosomes suggests a possible mechanism for PrP C transport in blood and for cellto-cell transmission. IntroductionCellular prion protein (PrP C ) is a membrane-bound, glycophosphatidylinositol (GPI)-anchored protein 1 found primarily in lipid rafts on the cell membrane of neuronal and non-neuronal cells, including tonsils, spleen, and of the secretory granules of epithelial cells in the stomach, as well as in cultured cell lines. 2,3 Although PrP C has been shown to be present on the surface of a number of peripheral blood cells, 4 the relative levels on individual cell types have been contentious. Individual studies have reported that the majority of PrP C is associated with both platelets 5,6 and red blood cells. 7 In the former case the surface expression of PrP C is increased following stimulation, suggesting an additional internal membrane source of the protein, 8 recently shown to be alpha granule membranes. 9 Furthermore, platelet activation is associated with the accumulation of PrP C in releasates, 10 and in platelet concentrates, stored for up to 10 days, there is an increase in initially the microsomal, then plasma levels of PrP C . 11 Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative disorders, including CreutzfeldtJakob disease (CJD), Gerstmann-Straussler-Schienker syndrome, and fatal familial insomnia in humans; scrapie in sheep; and bovine spongiform encephalopathy (BSE) in cattle. 12,13 They are all characterized by the accumulation of a proteaseresistant isomer (PrP Sc ) of PrP C in the brain of affected individuals. It is generally considered that PrP Sc acts as a template inducing the same structural changes within other normally folded PrP C molecules on contact, thus propagating the misfolded state of the protein. 14 The CNS is the site at which TSE pathology is apparent in prion infections; however, the agent must first replicate and be transported to the CNS after peripheral infection. The spread of PrP Sc has been tracked from the gas...

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Cellular prion protein is released on exosomes from activated platelets

Robertson

Booth

Beniac

et al. 2006

Blood

123

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“…Previous work showed that several types of blood cells express PrP, albeit at vastly different levels: lymphocytes, dendritic cells, monocytes, granulocytes, erythrocytes, platelets, certain lymphoid precursors, and CD34 ؉ cells, which in humans are an enriched stem͞progenitor cell population (7,(24)(25)(26)(27). However, it was unknown whether PrP is expressed on HSCs with repopulating activity, and there was no indication of a possible function of PrP in any of these cells.…”

Section: Discussionmentioning

confidence: 99%

Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal

Zhang

Steele

Lindquist

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

214

196

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“…PrP C is produced endogenously by cells of the platelet lineage, which could implicate platelets in PrP RES propagation or trafficking within the body or transmission in contaminated blood products (11,34,35,37,48). Forty-three to 53%, 63 to 95%, and 69 to 93% of bovine (3), ovine (4), and white-tailed deer (unpublished findings) platelets, respectively, express PrP C , and given the number of circulating platelets versus the number of leukocytes, the majority of blood-borne PrP C expression is platelet associated (11,48,71). This blood component could be largely responsible for the transmission of vCJD by transfusion (45,46).…”

Section: Interval To Detection Of Cwd Infection By Tonsil Biopsymentioning

confidence: 93%

B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease

Mathiason

Hayes-Klug

Hays

et al. 2010

J Virol

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Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cer- Chronic wasting disease (CWD) is an infectious proteinmisfolding disease, or transmissible spongiform encephalopathy (TSE), affecting cervids in North America (59, 76-79) and one Asian country (41,68). CWD is unique among prion diseases in affecting free-ranging wildlife populations (deer, elk, and moose). Early and subsequent observations made by Williams and Miller (58,79) related CWD transmission to direct contact with clinically affected deer, as well as indirect contact with environments previously populated by infected deer (57). Bioassay studies of white-tailed deer have demonstrated that body fluids and excreta (saliva, urine, feces, and blood) contain infectious prions (53, 54). Both clinical and preclinical CWDinfected deer harbored sufficient infectious prions to produce CWD in naïve white-tailed deer following ingestion of saliva or transfusion of whole blood (53, 54).The detection of blood-borne infectious prions has important implications for our understanding of the spread of prions among and within individuals, as well as for the elimination of prions from blood products (13,15,33,45), given the evidence for Creutzfeldt-Jakob disease (CJD) transmission via blood transfusion (16,29,47,50,62,72,73). Identifying the cell phenotype or cell-free protein fractions that harbor prion infectivity would contribute importantly to this understanding and to the development of blood-based assays to detect prion infection. We undertook the present studies to address these issues. MATERIALS AND METHODSBioassay studies of white-tailed deer. White-tailed deer fawns were provided by the Warnell School of Forestry and Natural Resources, University of Georgia, Athens-a region in which CWD has not been detected. The deer fawns were hand raised and human and indoor adapted before overnight transport directly to the Colorado State University (CSU) CWD research indoor isolation facility without contact with the native Colorado environment. The 4-month-old fawns were adapted to the facility housing conditions and diet for 2 months before the study start.Genotyping. All white-tailed deer were genotyped to determine their GG/GS (codon 96) status by the laboratory of Katherine O'Rourke, USDA-ARS, Pullman, WA. Deer were allocated into inoculation cohorts (n ϭ 4) without knowledge of their G96 genotypes.Biocontainment protocols. Protocols to preclude extraneous exposure and cross contamination between cohorts of animals as previously described (53, 54) incorporated protective shower-in requirements, Tyvek clothing, masks, head covers, and footwear while maintaining stringent husbandry. Tonsil biopsy ...

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The expression of prion protein (PrPC) in the megakaryocyte lineage

Cited by 29 publications

References 26 publications

Cellular prion protein is released on exosomes from activated platelets

Cellular prion protein is released on exosomes from activated platelets

Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal

B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease

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