Bovine Prion Is Endocytosed by Human Enterocytes via the 37 kDa/67 kDa Laminin Receptor

Morel, Étienne; Andrieu, Thibault; Casagrande, Fabrice; Gauczynski, Sabine; Weiß, Stefan; Grassi, Jacques; Rousset, Monique; Dormont, Dominique; Chambaz, Jean

doi:10.1016/s0002-9440(10)61192-3

Cited by 95 publications

(91 citation statements)

References 45 publications

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“…[16][17][18] expressing enterocytes. Enterocytes are the major cell population of the intestinal epithelium and due to their ability to endocytose pathogens, nutrients and macromolecules, 19 it has been proposed that these cells may represent a major entry site for alimentary prions (Fig. 1).…”

Section: Alimentary Prion Infectionsmentioning

confidence: 99%

Alimentary prion infections

Dias

Jovanović²,

Weiß³

2011

Prion

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N eurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of β-sheets that accumulate in the central nervous system. These diseases, including Morbus Alzheimer, Parkinson disease and Transmissible Spongiform Encephalopathies (TSEs)-also termed prion disorders-afflict a substantial proportion of the human population and, as such, the etiology and pathogenesis of these diseases has been the focus of mounting research. Although many of these diseases arise from genetic mutations or are sporadic in nature, the possible horizontal transmissibility of neurodegenerative diseases poses a great threat to population health. In this article we discuss recent studies that suggest that the "non-transmissible" status bestowed upon Alzheimer and Parkinson diseases may need to be revised as these diseases have been successfully induced through tissue transplants. Furthermore, we highlight the importance of investigating the "natural" mechanism of prion transmission including peroral and perenteral transmission, proposed routes of gastrointestinal uptake and neuroinvasion of ingested infectious prion proteins. We examine the multitude of factors which may influence oral transmissibility and discuss the zoonotic threats that Chronic Wasting disease (CWD), Bovine Spongiform Encephalopathy (BSE) and Scrapie may pose resulting in vCJD or related disorders. In addition, we suggest that the 37 kDa/67 kDa laminin receptor on the cell surface of enterocytes, a major cell population in

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Section: Alimentary Prion Infectionsmentioning

confidence: 99%

Alimentary prion infections

Dias

Jovanović²,

Weiß³

2011

Prion

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“…It has been shown that PrP interacts with these proteins in cis-interactions through its N-terminal tail. Importantly, the laminin receptor is also involved in the binding [24] and the endocytosis of the pathological isoform of PrP, protease resistant isoform of PrP (PrPres) [25]. Although, the precise nature of the binding sites remains to be established, none of the previously described PrP partners could account for the binding described here in immune cells.…”

Section: Discussionmentioning

confidence: 91%

Expression profiles of prion and doppel proteins and of their receptors in mouse splenocytes

et al. 2008

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Doppel (Dpl) shares common structural features with the prion protein (PrP) whose pathologic isoform is considered as the causative agent of prion diseases. Although their physiological functions in the immune system remain largely unknown, we demonstrated that substantial amounts of PrP and Dpl are expressed by spleen cells notably B lymphocytes, granulocytes and DC, but not T lymphocytes and NK. To characterize transinteracting partners of PrP and Dpl on mouse splenocytes, fluorescent PrP and Dpl tetramers were produced and used as tracers. Both tetramers specifically bind to B lymphocytes, dendritic cells, macrophages and granulocytes and in a lesser extend to T lymphocytes. No binding was observed on NK, follicular dendritic cells and mesenchymal spleen cells. The activation of intracellular transduction signals (i.e. intracellular calcium concentration and activation of the MAP kinase pathway) suggested that PrP and Dpl tetramers bind to functional receptors on B cells. None of the previously described PrP partners account for the binding sites characterized here. Our study suggests a possible role for PrP and Dpl in the cell-cell interactions in the immune system.

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“…4) located at the cell surface and is soluble in the cytoplasm and in the nucleus. At the cell surface the protein serves as a receptor for a variety of substrates including: ECM components such as elastin and laminin; viruses including Sindbis 92 Dengue, 93 Venezuelan equine encephalitis and Adeno-associated virus subtypes 2, 3, 8 and 9, 31,32 as well as cellular 73 and infectious prion proteins 72,74,75 (Fig. 5).…”

Section: The 37 Kda/67 Kda Laminin Receptor Precursor/ Laminin Receptormentioning

confidence: 99%

“…PrP c constitutively cycles between the cell membrane and intra-cellular compartments via the endocytic pathway-a process mediated by the 37 kDa/67 kDa Laminin Receptor Precursor, 72 a high affinity receptor for PrP c73 and PrP Sc . 72,[74][75][76] The prion variants share a common amino acid sequence and differ primarily with regards to secondary structure (PrP Sc exhibits greater β sheet proportion than PrP c -consistent with its higher aggregation propensity) and proteinase K digestion (PrP Sc resists degradation while PrP c does not). 71,77 PrP c has a multitude of physiological functions 70 and the majority of these functions are dependent on the interaction of the prion protein with an array (>70)of proteins.…”

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confidence: 99%