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Sci Rep. 2018 Jun 5;8(1):8654. doi: 10.1038/s41598-018-26685-x.

The prion protein is embedded in a molecular environment that modulates transforming growth factor β and integrin signaling.

Author information

1
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Centre, 6th Floor, 60 Leonard Avenue, Toronto, Ontario, M5T 0S8, Canada.
2
Department of Laboratory Medicine & Pathobiology, University of Toronto, Medical Sciences Building, 6th Floor, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
3
Department of Biochemistry, University of Toronto, Medical Sciences Building, 5th Floor, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
4
Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Research Tower, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
5
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Centre, 6th Floor, 60 Leonard Avenue, Toronto, Ontario, M5T 0S8, Canada. g.schmittulms@utoronto.ca.
6
Department of Laboratory Medicine & Pathobiology, University of Toronto, Medical Sciences Building, 6th Floor, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. g.schmittulms@utoronto.ca.

Abstract

At times, it can be difficult to discern if a lack of overlap in reported interactions for a protein-of-interest reflects differences in methodology or biology. In such instances, systematic analyses of protein-protein networks across diverse paradigms can provide valuable insights. Here, we interrogated the interactome of the prion protein (PrP), best known for its central role in prion diseases, in four mouse cell lines. Analyses made use of identical affinity capture and sample processing workflows. Negative controls were generated from PrP knockout lines of the respective cell models, and the relative levels of peptides were quantified using isobaric labels. The study uncovered 26 proteins that reside in proximity to PrP. All of these proteins are predicted to have access to the outer face of the plasma membrane, and approximately half of them were not reported to interact with PrP before. Strikingly, although several proteins exhibited profound co-enrichment with PrP in a given model, except for the neural cell adhesion molecule 1, no protein was highly enriched in all PrP-specific interactomes. However, Gene Ontology analyses revealed a shared association of the majority of PrP candidate interactors with cellular events at the intersection of transforming growth factor β and integrin signaling.

PMID:
29872131
PMCID:
PMC5988664
DOI:
10.1038/s41598-018-26685-x
[Indexed for MEDLINE]
Free PMC Article

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