Free access
Vet. Res.
Volume 39, Number 4, July-August 2008
Prion diseases in animals
Number of page(s) 16
Published online 27 November 2007
How to cite this article Vet. Res. (2008) 39:09
How to cite this article: Vet. Res. (2008) 39:09
DOI: 10.1051/vetres:2007048


Physiological role of the cellular prion protein

Viviana Zomosa-Signoret1, Jacques-Damien Arnaud2, Pascaline Fontes3, Maria-Terresa Alvarez-Martinez2 and Jean-Pierre Liautard1, 2

1  CPBS, UMR 5236, CC 100, Université Montpellier, 2 Place E. Bataillon, 34095 Montpellier Cedex, France
2  IFR-122, CC 100, Université Montpellier 2, Place E. Bataillon, 34095 Montpellier Cedex, France
3  CECEMA, Université Montpellier 2, Place E. Bataillon, 34095 Montpellier Cedex, France

Received 10 May 2007; accepted 21 September 2007; published online 27 November 2007

Abstract - The prion protein (PrP) plays a key role in the pathogenesis of prion diseases. However, the normal function of the protein remains unclear. The cellular isoform (PrPC) is expressed most abundantly in the brain, but has also been detected in other non-neuronal tissues as diverse as lymphoid cells, lung, heart, kidney, gastrointestinal tract, muscle, and mammary glands. Cell biological studies of PrP contribute to our understanding of PrP$^{\rm C}$ function. Like other membrane proteins, PrP$^{\rm C}$ is post-translationally processed in the endoplasmic reticulum and Golgi on its way to the cell surface after synthesis. Cell surface PrP$^{\rm C}$ constitutively cycles between the plasma membrane and early endosomes via a clathrin-dependent mechanism, a pathway consistent with a suggested role for PrP$^{\rm C}$ in cellular trafficking of copper ions. Although PrP-/- mice have been reported to have only minor alterations in immune function, PrP$^{\rm C}$ is up-regulated in T cell activation and may be expressed at higher levels by specialized classes of lymphocytes. Furthermore, antibody cross-linking of surface PrP$^{\rm C}$ modulates T cell activation and leads to rearrangements of lipid raft constituents and increased phosphorylation of signaling proteins. These findings appear to indicate an important but, as yet, ill-defined role in T cell function. Recent work has suggested that PrP$^{\rm C}$ is required for self-renewal of haematopoietic stem cells. PrP$^{\rm C}$ is highly expressed in the central nervous system, and since this is the major site of prion pathology, most interest has focused on defining the role of PrP$^{\rm C}$ in neurones. Although PrP-/- mice have a grossly normal neurological phenotype, even when neuronal PrP$^{\rm C}$ is knocked out postnatally, they do have subtle abnormalities in synaptic transmission, hippocampal morphology, circadian rhythms, and cognition and seizure threshold. Other postulated neuronal roles for PrP$^{\rm C}$ include copper-binding, as an anti- and conversely, pro-apoptotic protein, as a signaling molecule, and in supporting neuronal morphology and adhesion. The prion protein may also function as a metal binding protein such as copper, yielding cellular antioxidant capacity suggesting a role in the oxidative stress homeostasis. Finally, recent observations on the role of PrP$^{\rm C}$ in long-term memory open a challenging field.

Key words: prion / PrP$^{\rm C}$ / physiology / biology

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© INRA, EDP Sciences 2008