The cellular prion protein PrPc is expressed in human enterocytes in cell-cell junctional domains.
The physiological function of PrPc, the cellular isoform of prion protein, still remains unclear, although it has been established, in vitro or by using nerve cells, that it can homodimerize, bind copper, or interact with other proteins. Expression of PrPc was demonstrated as necessary for prion infection propagation. Considering the importance of the intestinal barrier in the process of oral prion infectivity, we have analyzed the expression of PrPc in enterocytes, which represent the major cell population of the intestinal epithelium. Our study, conducted both on normal human intestinal tissues and on the enterocytic cell line Caco-2/TC7, shows for the first time that PrPc is present in enterocytes. Interestingly, we found that this glycosylphosphatidylinositol-anchored glycoprotein was localized in cholesterol-dependent raft domains of the upper lateral membranes of enterocytes, beneath tight junctions, in cell-cell junctional domains. We observed that PrPc, E-cadherin, and Src co-localized in adherens junctions and that PrPc was co-immunoprecipitated with Src kinase but not with E-cadherin. Alteration of cell polarity after cholesterol depletion or loosening of the cell-cell junctions after EGTA treatment rapidly impaired membrane targeting of PrPc. Overall, our results point out the signaling of cell-cell contacts as a putative role for PrPc in epithelial cells.
INSERM U505, Université Pierre et Marie Curie, 15 Rue de l'Ecole de Médecine 75006 Paris.
Etienne
E
Morel
Stephane
S
Fouquet
Danielle
D
Chateau
Lucile
L
Yvernault
Yveline
Y
Frobert
Martine
M
Pincon-Raymond
Jean
J
Chambaz
Thierry
T
Pillot
Monique
M
Rousset
D022005:Adherens Junctions / Q000378:metabolism; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003300:Copper / Q000737:chemistry; D019281:Dimerization; D020895:Enterocytes / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D018621:PrPC Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D019061:src-Family Kinases / Q000378:metabolism
D015820:Cadherins; D006023:Glycoproteins; D018621:PrPC Proteins; D020033:Protein Isoforms; D003300:Copper; D002784:Cholesterol; D019061:src-Family Kinases