Issue |
Vet. Res.
Volume 39, Number 4, July-August 2008
Prion diseases in animals
|
|
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Number of page(s) | 16 | |
DOI | https://doi.org/10.1051/vetres:2007048 | |
Published online | 27 November 2007 | |
How to cite this article | Vet. Res. (2008) 39:09 |
DOI: 10.1051/vetres:2007048
Review
Physiological role of the cellular prion protein
Viviana Zomosa-Signoret1, Jacques-Damien Arnaud2, Pascaline Fontes3, Maria-Terresa Alvarez-Martinez2 and Jean-Pierre Liautard1, 21 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 function. Like other membrane proteins, PrP
is
post-translationally processed in the endoplasmic reticulum and Golgi on its
way to the cell surface after synthesis. Cell surface PrP
constitutively cycles between the plasma membrane and early endosomes via a
clathrin-dependent mechanism, a pathway consistent with a suggested role for
PrP
in cellular trafficking of copper ions. Although PrP-/- mice
have been reported to have only minor alterations in immune function,
PrP
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
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
is required for self-renewal of haematopoietic stem cells.
PrP
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
in neurones. Although PrP-/- mice have a grossly
normal neurological phenotype, even when neuronal PrP
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
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
in
long-term memory open a challenging field.
Key words: prion / PrP

Corresponding author: liautard@univ-montp2.fr
© INRA, EDP Sciences 2008