The cellular prion protein PrP(c) is involved in the proliferation of epithelial cells and in the distribution of junction-associated proteins.

PloS One
Etienne MorelCaroline Clair

Abstract

The physiological function of the ubiquitous cellular prion protein, PrP(c), is still under debate. It was essentially studied in nervous system, but poorly investigated in epithelial cells. We previously reported that PrP(c) is targeted to cell-cell junctions of polarized epithelial cells, where it interacts with c-Src. We show here that, in cultured human enterocytes and in intestine in vivo, the mature PrP(c) is differentially targeted either to the nucleus in dividing cells or to cell-cell contacts in polarized/differentiated cells. By proteomic analysis, we demonstrate that the junctional PrP(c) interacts with cytoskeleton-associated proteins, such as gamma- and beta-actin, alpha-spectrin, annexin A2, and with the desmosome-associated proteins desmoglein, plakoglobin and desmoplakin. In addition, co-immunoprecipitation experiments revealed complexes associating PrP(c), desmoglein and c-Src in raft domains. Through siRNA strategy, we show that PrP(c) is necessary to complete the process of epithelial cell proliferation and for the sub-cellular distribution of proteins involved in cell architecture and junctions. Moreover, analysis of the architecture of the intestinal epithelium of PrP(c) knock-out mice revealed a net decre...Continue Reading

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Citations

Apr 1, 2014·Acta Biochimica Et Biophysica Sinica·Xiaowen YangChaoyang Li
Dec 22, 2012·Expert Review of Proteomics·Edmondo CampisiMaurizio Pocchiari
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Feb 6, 2017·Molecular Cancer·Catharina MelzerRalf Hass
Apr 22, 2017·Frontiers in Molecular Biosciences·Andrew R Castle, Andrew C Gill
Jul 15, 2015·Journal of Cell Science·Dion D RichardsonMar Fernandez-Borja

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Methods Mentioned

BETA
transfection
immunoprecipitations
glycosylation
immunoprecipitation
co-immunoprecipitation
electron microscopy

Software Mentioned

PD Quest
Image Quant
Gatan
PHENYX
Axiovision
MASCOT

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