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Deletion of the amino‐terminal domain of the prion protein does not impair prion protein–dependent neuronal differentiation and neuritogenesis
Author(s) -
Barenco Maria Grazia,
Valori Chiara F.,
Roncoroni Chiara,
Loewer Johannes,
Montrasio Fabio,
Rossi Daniela
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21894
Subject(s) - microbiology and biotechnology , biology , cell culture , cellular differentiation , signal transduction , prion protein , biochemistry , genetics , gene , medicine , disease , pathology
Abstract The cellular prion protein (PrP C ) is a highly conserved glycoprotein of unknown biological function. To gain insight into the physiological role of PrP C , we generated a novel PrP knockout cell line, named PrP o/o ML, by immortalization of neuroepithelial precursor cells derived from the cerebellum of PrP‐knockout mice using the temperature‐sensitive simian virus 40 (SV40) large T antigen. We demonstrated that the PrP o/o ML cell line is a unipotent precursor line with glutamatergic properties, which can acquire neuronal features when cultivated under specific conditions. The role of the prion protein in the process of neuronal differentiation was then analyzed in the PrP o/o ML cells reconstituted with either the full‐length or an amino‐terminally deleted form of the prion protein. We show that the expression of PrP C facilitates the processes of neuronal differentiation and neuritogenesis and that the deletion of its amino‐terminal domain reduces the efficiency, but does not suppress this activity. This cell line represents a useful tool for studying PrP‐dependent signal transduction pathways during differentiation of neuronal stem/precursor cells. © 2008 Wiley‐Liss, Inc.