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

Abstract

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.

Prion Disease and the Innate Immune System

“…Gene expression data reveal that PrP expression is generally down-regulated during granulocyte differentiation [151] though some expression is still detectable [152] (see also Figure 2). Neutrophil functions have been shown to be inhibited by both native and scrapie associated prion protein, resulting in failure of neutrophil aggregation and deficits in superoxide radical and beta-glucuronidase export [153].…”

The Prion‐like Protein Doppel Enhances Ovine Spermatozoa Fertilizing Ability

“…Reports linking Doppel protein to the control of Ca 2+ movements in local cell domains, such as the endoplasmic reticulum and the mitochondrial matrix or beneath the plasma membrane, have emerged (Brini et al. 2005; Cordier‐Dirikoc et al. 2008).…”

“…However, observations in cells and tissues suggest that Doppel may also exist as an intracellular form devoid of the GPI anchor (Peoc’h et al. 2002; Cordier‐Dirikoc et al. 2008).…”

PRND (Prion Protein 2 (Dublet))

“…Additionally, Doppel is expressed with PrP C in spleen cells, notably B lymphocytes, granulocytes and dendritic cells (Cordier-Dirikoc et al, 2008).…”

“…The detection of Prnd mRNA in brain blood vessel endothelial cells might indicate a possible role in the development of brain blood vessels (Li et al, 2000). The observation that Doppel is expressed with PrP C in B lymphocytes, granulocytes and dendritic cells argues for a role in cell-cell interaction in the immunosystem (Cordier-Dirikoc et al, 2008). Several evidence showed that Doppel is able to coordinate in vitro the binding of copper ions with high affinity (Cereghetti et al, 2004;La Mendola et al, 2010;Qin et al, 2003).…”