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Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels
Misfolding, aggregation and accumulation of proteins are toxic elements in the progression of a broad range of neurodegenerative diseases. Molecular chaperones enable a cellular defense by reducing or compartmentalizing these insults. Small heat shock proteins (sHsps) engage proteins early in the pr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432035/ https://www.ncbi.nlm.nih.gov/pubmed/32751642 http://dx.doi.org/10.3390/ijms21155442 |
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author | Webster, Jack M. Darling, April L. Sanders, Taylor A. Blazier, Danielle M. Vidal-Aguiar, Yamile Beaulieu-Abdelahad, David Plemmons, Drew G. Hill, Shannon E. Uversky, Vladimir N. Bickford, Paula C. Dickey, Chad A. Blair, Laura J. |
author_facet | Webster, Jack M. Darling, April L. Sanders, Taylor A. Blazier, Danielle M. Vidal-Aguiar, Yamile Beaulieu-Abdelahad, David Plemmons, Drew G. Hill, Shannon E. Uversky, Vladimir N. Bickford, Paula C. Dickey, Chad A. Blair, Laura J. |
author_sort | Webster, Jack M. |
collection | PubMed |
description | Misfolding, aggregation and accumulation of proteins are toxic elements in the progression of a broad range of neurodegenerative diseases. Molecular chaperones enable a cellular defense by reducing or compartmentalizing these insults. Small heat shock proteins (sHsps) engage proteins early in the process of misfolding and can facilitate their proper folding or refolding, sequestration, or clearance. Here, we evaluate the effects of the sHsp Hsp22, as well as a pseudophosphorylated mutant and an N-terminal domain deletion (NTDΔ) variant on tau aggregation in vitro and tau accumulation and aggregation in cultured cells. Hsp22 wild-type (WT) protein had a significant inhibitory effect on heparin-induced aggregation in vitro and the pseudophosphorylated mutant Hsp22 demonstrated a similar effect. When co-expressed in a cell culture model with tau, these Hsp22 constructs significantly reduced soluble tau protein levels when transfected at a high ratio relative to tau. However, the Hsp22 NTDΔ protein drastically reduced the soluble protein expression levels of both tau WT and tau P301L/S320F even at lower transfection ratios, which resulted in a correlative reduction of the triton-insoluble tau P301L/S320F aggregates. |
format | Online Article Text |
id | pubmed-7432035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74320352020-08-24 Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels Webster, Jack M. Darling, April L. Sanders, Taylor A. Blazier, Danielle M. Vidal-Aguiar, Yamile Beaulieu-Abdelahad, David Plemmons, Drew G. Hill, Shannon E. Uversky, Vladimir N. Bickford, Paula C. Dickey, Chad A. Blair, Laura J. Int J Mol Sci Article Misfolding, aggregation and accumulation of proteins are toxic elements in the progression of a broad range of neurodegenerative diseases. Molecular chaperones enable a cellular defense by reducing or compartmentalizing these insults. Small heat shock proteins (sHsps) engage proteins early in the process of misfolding and can facilitate their proper folding or refolding, sequestration, or clearance. Here, we evaluate the effects of the sHsp Hsp22, as well as a pseudophosphorylated mutant and an N-terminal domain deletion (NTDΔ) variant on tau aggregation in vitro and tau accumulation and aggregation in cultured cells. Hsp22 wild-type (WT) protein had a significant inhibitory effect on heparin-induced aggregation in vitro and the pseudophosphorylated mutant Hsp22 demonstrated a similar effect. When co-expressed in a cell culture model with tau, these Hsp22 constructs significantly reduced soluble tau protein levels when transfected at a high ratio relative to tau. However, the Hsp22 NTDΔ protein drastically reduced the soluble protein expression levels of both tau WT and tau P301L/S320F even at lower transfection ratios, which resulted in a correlative reduction of the triton-insoluble tau P301L/S320F aggregates. MDPI 2020-07-30 /pmc/articles/PMC7432035/ /pubmed/32751642 http://dx.doi.org/10.3390/ijms21155442 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Webster, Jack M. Darling, April L. Sanders, Taylor A. Blazier, Danielle M. Vidal-Aguiar, Yamile Beaulieu-Abdelahad, David Plemmons, Drew G. Hill, Shannon E. Uversky, Vladimir N. Bickford, Paula C. Dickey, Chad A. Blair, Laura J. Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels |
title | Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels |
title_full | Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels |
title_fullStr | Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels |
title_full_unstemmed | Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels |
title_short | Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels |
title_sort | hsp22 with an n-terminal domain truncation mediates a reduction in tau protein levels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432035/ https://www.ncbi.nlm.nih.gov/pubmed/32751642 http://dx.doi.org/10.3390/ijms21155442 |
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