From stem cells to prion signalling.
A strategy based upon the introduction of an adenovirus-SV40 plasmid into multipotential cells was designed to immortalize clones displaying properties of lineage stem cells. The murine 1C11 cell line behaves as a neuroepithelial progenitor. Upon appropriate induction, almost 100% of 1C11 precursor cells develop neurite extensions and convert into either serotonergic or noradrenergic neurons. The two mutually exclusive neuronal programs are autoregulated by serotonergic or adrenergic receptors. PrPc is constitutively expressed by 1C11 cells. Antibody-mediated cross-linking of PrPc promotes the dephosphorylation of the tyrosine kinase Fyn associated to a Fyn kinase activation. The coupling of PrPc to Fyn is dependent on caveolin-1. It is restricted to the fully differentiated serotonergic or noradrenergic cells and occurs mainly at neurites. Thus, PrPc may represent a signal transduction protein which may fine-tune neuronal functions. Since the 1C11 stem cell supports prion replication, it may provide a tool to investigate whether PrPSc accumulation interferes with PrPc signalling activity.
Kellermann
Odile
O
Laboratoire de différenciation cellulaire et prions, CNRS UPR 1983-Institut Pasteur, BP 8, 94801 Villejuif, France. okellerm@vjf.cnrs.fr
Lafay-Chebassier
Claire
C
Ermonval
Myriam
M
Lehmann
Sylvain
S
Mouillet-Richard
Sophie
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D015870:Gene Expression; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics* / Q000502:physiology; D011328:Prions / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction; D013539:Simian virus 40 / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection
C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D018621:PrPC Proteins; D011328:Prions; D011518:Proto-Oncogene Proteins; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn