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


RESULTS
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 decrease in the size of desmosomal junctions and, without change in the amount of BrdU incorporation, a shortening of the length of intestinal villi.


CONCLUSIONS
From these results, PrP(c) could be considered as a new partner involved in the balance between proliferation and polarization/differentiation in epithelial cells.
Morel
Etienne
E
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris, F-75006 France.
Fouquet
Stéphane
S
Strup-Perrot
Carine
C
Pichol Thievend
Cathy
C
Thievend
Cathy Pichol
CP
Petit
Constance
C
Loew
Damarys
D
Faussat
Anne-Marie
AM
Yvernault
Lucile
L
Pinçon-Raymond
Martine
M
Chambaz
Jean
J
Rousset
Monique
M
Thenet
Sophie
S
Clair
Caroline
C
D018938:Caco-2 Cells; D002455:Cell Division / Q000502:physiology*; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D008055:Lipids / Q000494:pharmacology; D010957:Plasmids; D018621:PrPC Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
D008055:Lipids; D018621:PrPC Proteins; D034741:RNA, Small Interfering; C484027:oligofectamine