The Cellular Prion Protein: A Player in Immunological Quiescence

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2015 Sep 22

PMID 26388873

Citations 26

Authors

Maren K Bakkebo

Sophie Mouillet-Richard

Arild Espenes

Wilfred Goldmann

Jorg Tatzelt

Michael A Tranulis

Affiliations

Soon will be listed here.

Abstract

Despite intensive studies since the 1990s, the physiological role of the cellular prion protein (PrP(C)) remains elusive. Here, we present a novel concept suggesting that PrP(C) contributes to immunological quiescence in addition to cell protection. PrP(C) is highly expressed in diverse organs that by multiple means are particularly protected from inflammation, such as the brain, eye, placenta, pregnant uterus, and testes, while at the same time it is expressed in most cells of the lymphoreticular system. In this paradigm, PrP(C) serves two principal roles: to modulate the inflammatory potential of immune cells and to protect vulnerable parenchymal cells against noxious insults generated through inflammation. Here, we review studies of PrP(C) physiology in view of this concept.

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References

Resenberger U, Harmeier A, Woerner A, Goodman J, Muller V, Krishnan R . The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication. EMBO J. 2011; 30(10):2057-70. PMC: 3098494. DOI: 10.1038/emboj.2011.86. View

Tobler I, Gaus S, Deboer T, Achermann P, Fischer M, Rulicke T . Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature. 1996; 380(6575):639-42. DOI: 10.1038/380639a0. View

Roffe M, Beraldo F, Bester R, Nunziante M, Bach C, Mancini G . Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR. Proc Natl Acad Sci U S A. 2010; 107(29):13147-52. PMC: 2919922. DOI: 10.1073/pnas.1000784107. View

Haddon D, Hughes M, Antignano F, Westaway D, Cashman N, McNagny K . Prion protein expression and release by mast cells after activation. J Infect Dis. 2009; 200(5):827-31. DOI: 10.1086/605022. View

Altmeppen H, Prox J, Krasemann S, Puig B, Kruszewski K, Dohler F . The sheddase ADAM10 is a potent modulator of prion disease. Elife. 2015; 4. PMC: 4346534. DOI: 10.7554/eLife.04260. View

Viegas P, Chaverot N, Enslen H, Perriere N, Couraud P, Cazaubon S . Junctional expression of the prion protein PrPC by brain endothelial cells: a role in trans-endothelial migration of human monocytes. J Cell Sci. 2006; 119(Pt 22):4634-43. DOI: 10.1242/jcs.03222. View

Bueler H, Fischer M, Lang Y, Bluethmann H, Lipp H, DeArmond S . Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature. 1992; 356(6370):577-82. DOI: 10.1038/356577a0. View

Mattei V, Garofalo T, Misasi R, Circella A, Manganelli V, Lucania G . Prion protein is a component of the multimolecular signaling complex involved in T cell activation. FEBS Lett. 2004; 560(1-3):14-8. DOI: 10.1016/S0014-5793(04)00029-8. View

Bechmann I, Galea I, Perry V . What is the blood-brain barrier (not)?. Trends Immunol. 2006; 28(1):5-11. DOI: 10.1016/j.it.2006.11.007. View

10.

Burthem J, Urban B, Pain A, Roberts D . The normal cellular prion protein is strongly expressed by myeloid dendritic cells. Blood. 2001; 98(13):3733-8. DOI: 10.1182/blood.v98.13.3733. View

11.

Stewart P, Campbell L, Skogtvedt S, Griffin K, Arnemo J, Tryland M . Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region. PLoS One. 2012; 7(12):e50623. PMC: 3517517. DOI: 10.1371/journal.pone.0050623. View

12.

Tanji K, Saeki K, Takeda M, Hirasawa K, Doi K, Matsumoto Y . Analysis of PrPc mRNA by in situ hybridization in brain, placenta, uterus and testis of rats. Intervirology. 1995; 38(6):309-15. DOI: 10.1159/000150457. View

13.

Donne D, Viles J, Groth D, Mehlhorn I, James T, Cohen F . Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible. Proc Natl Acad Sci U S A. 1998; 94(25):13452-7. PMC: 28326. DOI: 10.1073/pnas.94.25.13452. View

14.

Liao Y, Lebo R, Clawson G, SMUCKLER E . Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications. Science. 1986; 233(4761):364-7. DOI: 10.1126/science.3014653. View

15.

Fujisaki J, Wu J, Carlson A, Silberstein L, Putheti P, Larocca R . In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011; 474(7350):216-9. PMC: 3725645. DOI: 10.1038/nature10160. View

16.

Resenberger U, Winklhofer K, Tatzelt J . Neuroprotective and neurotoxic signaling by the prion protein. Top Curr Chem. 2011; 305:101-19. DOI: 10.1007/128_2011_160. View

17.

Mani K, Cheng F, Havsmark B, Jonsson M, Belting M, Fransson L . Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate. J Biol Chem. 2003; 278(40):38956-65. DOI: 10.1074/jbc.M300394200. View

18.

Bertuchi F, Bourgeon D, Landemberger M, Martins V, Cerchiaro G . PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice. Biochem Biophys Res Commun. 2012; 418(1):27-32. DOI: 10.1016/j.bbrc.2011.12.098. View

19.

Brown D, Besinger A, Herms J, Kretzschmar H . Microglial expression of the prion protein. Neuroreport. 1998; 9(7):1425-9. DOI: 10.1097/00001756-199805110-00032. View

20.

Chen S, Teplow D, Parchi P, Teller J, Gambetti P . Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem. 1995; 270(32):19173-80. DOI: 10.1074/jbc.270.32.19173. View