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Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin
The cellular prion protein (PrP(C)) is renowned for its infectious conformational isoform PrP(Sc), capable of templating subsequent conversions of healthy PrP(C)s and thus triggering the group of incurable diseases known as transmissible spongiform encephalopathies. Besides this mechanism not being...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704586/ https://www.ncbi.nlm.nih.gov/pubmed/34940479 http://dx.doi.org/10.3390/membranes11120978 |
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author | Dondapati, Divya Teja Cingaram, Pradeep Reddy Ayaydin, Ferhan Nyeste, Antal Kanyó, Andor Welker, Ervin Fodor, Elfrieda |
author_facet | Dondapati, Divya Teja Cingaram, Pradeep Reddy Ayaydin, Ferhan Nyeste, Antal Kanyó, Andor Welker, Ervin Fodor, Elfrieda |
author_sort | Dondapati, Divya Teja |
collection | PubMed |
description | The cellular prion protein (PrP(C)) is renowned for its infectious conformational isoform PrP(Sc), capable of templating subsequent conversions of healthy PrP(C)s and thus triggering the group of incurable diseases known as transmissible spongiform encephalopathies. Besides this mechanism not being fully uncovered, the protein’s physiological role is also elusive. PrP(C) and its newest, less understood paralog Shadoo are glycosylphosphatidylinositol-anchored proteins highly expressed in the central nervous system. While they share some attributes and neuroprotective actions, opposing roles have also been reported for the two; however, the amount of data about their exact functions is lacking. Protein–protein interactions and membrane microdomain localizations are key determinants of protein function. Accurate identification of these functions for a membrane protein, however, can become biased due to interactions occurring during sample processing. To avoid such artifacts, we apply a non-detergent-based membrane-fractionation approach to study the prion protein and Shadoo. We show that the two proteins occupy similarly raft and non-raft membrane fractions when expressed in N2a cells and that both proteins pull down the chaperone calnexin in both rafts and non-rafts. These indicate their possible binding to calnexin in both types of membrane domains, which might be a necessary requisite to aid the inherently unstable native conformation during their lifetime. |
format | Online Article Text |
id | pubmed-8704586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87045862021-12-25 Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin Dondapati, Divya Teja Cingaram, Pradeep Reddy Ayaydin, Ferhan Nyeste, Antal Kanyó, Andor Welker, Ervin Fodor, Elfrieda Membranes (Basel) Article The cellular prion protein (PrP(C)) is renowned for its infectious conformational isoform PrP(Sc), capable of templating subsequent conversions of healthy PrP(C)s and thus triggering the group of incurable diseases known as transmissible spongiform encephalopathies. Besides this mechanism not being fully uncovered, the protein’s physiological role is also elusive. PrP(C) and its newest, less understood paralog Shadoo are glycosylphosphatidylinositol-anchored proteins highly expressed in the central nervous system. While they share some attributes and neuroprotective actions, opposing roles have also been reported for the two; however, the amount of data about their exact functions is lacking. Protein–protein interactions and membrane microdomain localizations are key determinants of protein function. Accurate identification of these functions for a membrane protein, however, can become biased due to interactions occurring during sample processing. To avoid such artifacts, we apply a non-detergent-based membrane-fractionation approach to study the prion protein and Shadoo. We show that the two proteins occupy similarly raft and non-raft membrane fractions when expressed in N2a cells and that both proteins pull down the chaperone calnexin in both rafts and non-rafts. These indicate their possible binding to calnexin in both types of membrane domains, which might be a necessary requisite to aid the inherently unstable native conformation during their lifetime. MDPI 2021-12-13 /pmc/articles/PMC8704586/ /pubmed/34940479 http://dx.doi.org/10.3390/membranes11120978 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dondapati, Divya Teja Cingaram, Pradeep Reddy Ayaydin, Ferhan Nyeste, Antal Kanyó, Andor Welker, Ervin Fodor, Elfrieda Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin |
title | Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin |
title_full | Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin |
title_fullStr | Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin |
title_full_unstemmed | Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin |
title_short | Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin |
title_sort | membrane domain localization and interaction of the prion-family proteins, prion and shadoo with calnexin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704586/ https://www.ncbi.nlm.nih.gov/pubmed/34940479 http://dx.doi.org/10.3390/membranes11120978 |
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