edoc-vmtest

Functionally relevant domains of the prion protein identified in vivo

Baumann, Frank and Pahnke, Jens and Radovanovic, Ivan and Rülicke, Thomas and Bremer, Juliane and Tolnay, Markus and Aguzzi, Adriano. (2009) Functionally relevant domains of the prion protein identified in vivo. PLoS one, Vol. 4 , e6707.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6003038

Downloads: Statistics Overview

Abstract

The prion consists essentially of PrP(Sc), a misfolded and aggregated conformer of the cellular protein PrP(C). Whereas PrP(C) deficient mice are clinically healthy, expression of PrP(C) variants lacking its central domain (PrP(DeltaCD)), or of the PrP-related protein Dpl, induces lethal neurodegenerative syndromes which are repressed by full-length PrP. Here we tested the structural basis of these syndromes by grafting the amino terminus of PrP(C) (residues 1-134), or its central domain (residues 90-134), onto Dpl. Further, we constructed a soluble variant of the neurotoxic PrP(DeltaCD) mutant that lacks its glycosyl phosphatidyl inositol (GPI) membrane anchor. Each of these modifications abrogated the pathogenicity of Dpl and PrP(DeltaCD) in transgenic mice. The PrP-Dpl chimeric molecules, but not anchorless PrP(DeltaCD), ameliorated the disease of mice expressing truncated PrP variants. We conclude that the amino proximal domain of PrP exerts a neurotrophic effect even when grafted onto a distantly related protein, and that GPI-linked membrane anchoring is necessary for both beneficial and deleterious effects of PrP and its variants.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Allgemeine Pathologie (Tolnay)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Allgemeine Pathologie (Tolnay)
UniBasel Contributors:Tolnay, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:13

Repository Staff Only: item control page