title: The cellular prion protein PrP(c) is involved in the proliferation of epithelial cells and in the distribution of junction-associated proteins.
abstract: 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.
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris, F-75006 France.
authors: Etienne
authors: E
authors: Morel
authors: Stéphane
authors: S
authors: Fouquet
authors: Carine
authors: C
authors: Strup-Perrot
authors: Cathy
authors: C
authors: Pichol Thievend
authors: Cathy Pichol
authors: CP
authors: Thievend
authors: Constance
authors: C
authors: Petit
authors: Damarys
authors: D
authors: Loew
authors: Anne-Marie
authors: AM
authors: Faussat
authors: Lucile
authors: L
authors: Yvernault
authors: Martine
authors: M
authors: Pinçon-Raymond
authors: Jean
authors: J
authors: Chambaz
authors: Monique
authors: M
authors: Rousset
authors: Sophie
authors: S
authors: Thenet
authors: Caroline
authors: C
authors: Clair
mesh_terms: 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
chemical_list: D008055:Lipids; D018621:PrPC Proteins; D034741:RNA, Small Interfering; C484027:oligofectamine