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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-17675

Rutishauser, D; Mertz, K D; Moos, R; Brunner, E; Rülicke, T; Calella, A M; Aguzzi, A (2009). The comprehensive native interactome of a fully functional tagged prion protein. PLoS ONE, 4(2):e4446.

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Abstract

The enumeration of the interaction partners of the cellular prion protein, PrP(C), may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrP(C). When expressed in transgenic mice, PrP(myc) carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrP(C). PrP(myc) antagonized the toxicity of truncated PrP, restored prion infectibility of PrP(C)-deficient mice, and was physically incorporated into PrP(Sc) aggregates, indicating that it possessed all functional characteristics of genuine PrP(C). We then immunopurified myc epitope-containing protein complexes from PrP(myc) transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrP(C) and may represent component of a multiprotein complex. Selected PrP(C) interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance.

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38 citations in Web of Science®
38 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
08 University Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:12 Mar 2009 09:52
Last Modified:12 Nov 2014 12:25
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
Publisher DOI:10.1371/journal.pone.0004446
PubMed ID:19209230

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