Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function. / Hosp, Fabian; Gutiérrez-Ángel, Sara; Schaefer, Martin H; Cox, Jürgen; Meissner, Felix; Hipp, Mark S; Hartl, F-Ulrich; Klein, Rüdiger; Dudanova, Irina; Mann, Matthias.

In: Cell Reports, Vol. 21, No. 8, 21.11.2017, p. 2291-2303.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hosp, F, Gutiérrez-Ángel, S, Schaefer, MH, Cox, J, Meissner, F, Hipp, MS, Hartl, F-U, Klein, R, Dudanova, I & Mann, M 2017, 'Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function', Cell Reports, vol. 21, no. 8, pp. 2291-2303. https://doi.org/10.1016/j.celrep.2017.10.097

APA

Hosp, F., Gutiérrez-Ángel, S., Schaefer, M. H., Cox, J., Meissner, F., Hipp, M. S., Hartl, F-U., Klein, R., Dudanova, I., & Mann, M. (2017). Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function. Cell Reports, 21(8), 2291-2303. https://doi.org/10.1016/j.celrep.2017.10.097

Vancouver

Hosp F, Gutiérrez-Ángel S, Schaefer MH, Cox J, Meissner F, Hipp MS et al. Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function. Cell Reports. 2017 Nov 21;21(8):2291-2303. https://doi.org/10.1016/j.celrep.2017.10.097

Author

Hosp, Fabian ; Gutiérrez-Ángel, Sara ; Schaefer, Martin H ; Cox, Jürgen ; Meissner, Felix ; Hipp, Mark S ; Hartl, F-Ulrich ; Klein, Rüdiger ; Dudanova, Irina ; Mann, Matthias. / Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function. In: Cell Reports. 2017 ; Vol. 21, No. 8. pp. 2291-2303.

Bibtex

@article{69a8649cd9f540deafaa8d1193527cbb,
title = "Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function",
abstract = "Aggregation of polyglutamine-expanded huntingtin exon 1 (HttEx1) in Huntington's disease (HD) proceeds from soluble oligomers to late-stage inclusions. The nature of the aggregates and how they lead to neuronal dysfunction is not well understood. We employed mass spectrometry (MS)-based quantitative proteomics to dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model of HD. Extensive remodeling of the soluble brain proteome correlated with insoluble aggregate formation during disease progression. In-depth and quantitative characterization of the aggregates uncovered an unprecedented complexity of several hundred proteins. Sequestration to aggregates depended on protein expression levels and sequence features such as low-complexity regions or coiled-coil domains. In a cell-based HD model, overexpression of a subset of the sequestered proteins in most cases rescued viability and reduced aggregate size. Our spatiotemporally resolved proteome resource of HD progression indicates that widespread loss of cellular protein function contributes to aggregate-mediated toxicity.",
keywords = "Journal Article",
author = "Fabian Hosp and Sara Guti{\'e}rrez-{\'A}ngel and Schaefer, {Martin H} and J{\"u}rgen Cox and Felix Meissner and Hipp, {Mark S} and F-Ulrich Hartl and R{\"u}diger Klein and Irina Dudanova and Matthias Mann",
note = "Copyright {\textcopyright} 2017 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = nov,
day = "21",
doi = "10.1016/j.celrep.2017.10.097",
language = "English",
volume = "21",
pages = "2291--2303",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",

}

RIS

TY - JOUR

T1 - Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function

AU - Hosp, Fabian

AU - Gutiérrez-Ángel, Sara

AU - Schaefer, Martin H

AU - Cox, Jürgen

AU - Meissner, Felix

AU - Hipp, Mark S

AU - Hartl, F-Ulrich

AU - Klein, Rüdiger

AU - Dudanova, Irina

AU - Mann, Matthias

N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2017/11/21

Y1 - 2017/11/21

N2 - Aggregation of polyglutamine-expanded huntingtin exon 1 (HttEx1) in Huntington's disease (HD) proceeds from soluble oligomers to late-stage inclusions. The nature of the aggregates and how they lead to neuronal dysfunction is not well understood. We employed mass spectrometry (MS)-based quantitative proteomics to dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model of HD. Extensive remodeling of the soluble brain proteome correlated with insoluble aggregate formation during disease progression. In-depth and quantitative characterization of the aggregates uncovered an unprecedented complexity of several hundred proteins. Sequestration to aggregates depended on protein expression levels and sequence features such as low-complexity regions or coiled-coil domains. In a cell-based HD model, overexpression of a subset of the sequestered proteins in most cases rescued viability and reduced aggregate size. Our spatiotemporally resolved proteome resource of HD progression indicates that widespread loss of cellular protein function contributes to aggregate-mediated toxicity.

AB - Aggregation of polyglutamine-expanded huntingtin exon 1 (HttEx1) in Huntington's disease (HD) proceeds from soluble oligomers to late-stage inclusions. The nature of the aggregates and how they lead to neuronal dysfunction is not well understood. We employed mass spectrometry (MS)-based quantitative proteomics to dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model of HD. Extensive remodeling of the soluble brain proteome correlated with insoluble aggregate formation during disease progression. In-depth and quantitative characterization of the aggregates uncovered an unprecedented complexity of several hundred proteins. Sequestration to aggregates depended on protein expression levels and sequence features such as low-complexity regions or coiled-coil domains. In a cell-based HD model, overexpression of a subset of the sequestered proteins in most cases rescued viability and reduced aggregate size. Our spatiotemporally resolved proteome resource of HD progression indicates that widespread loss of cellular protein function contributes to aggregate-mediated toxicity.

KW - Journal Article

U2 - 10.1016/j.celrep.2017.10.097

DO - 10.1016/j.celrep.2017.10.097

M3 - Journal article

C2 - 29166617

VL - 21

SP - 2291

EP - 2303

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 8

ER -

ID: 186194464