Deletion of the amino-terminal domain of the prion protein does not impair prion protein-dependent neuronal differentiation and neuritogenesis

Maria Grazia Barenco, Chiara F. Valori, Chiara Roncoroni, Johannes Loewer, Fabio Montrasio, Daniela Rossi

Research output: Contribution to journalArticle

Abstract

The cellular prion protein (PrPc) is a highly conserved glycoprotein of unknown biological function. To gain insight into the physiological role of PrPc, we generated a novel PrP knockout cell line, named PrP 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 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 ML cells reconstituted with either the full-length or an amino-terminally deleted form of the prion protein. We show that the expression of PrPc 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.

Original languageEnglish
Pages (from-to)806-819
Number of pages14
JournalJournal of Neuroscience Research
Volume87
Issue number3
DOIs
Publication statusPublished - Feb 15 2009

Keywords

  • Immortalization
  • Neuritogenesis
  • Neuronal differentiation
  • Prion protein
  • SV40 large T antigen

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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