Publication:
In Situ Architecture and Cellular Interactions of PolyQ Inclusions

Thumbnail Image
Files
Cell_2017a_author_manuscript.pdf(1.99 MB)
Date
2017-09-21
relationships.isAuthorOfPublication
relationships.isSecondaryAuthorOf
relationships.isDirectorOf
Authors
Bäuerlein, Felix ; Saha, Itika ; Mishra, Archana ; Kalemanov, Maria ; Martinez-Sanchez, Antonio ; Klein, Rudiger ; Dudanova, Irina ; Hipp, Mark ; Hartl, Ulrich ; Baumeister, Wolfgang ; Fernandez-Busnadiego, Ruben
item.page.secondaryauthor
item.page.director
Publisher
Elsevier
publication.page.editor
publication.page.department
IngenierĂ­a de la InformaciĂłn y las Comunicaciones
DOI
https://doi.org/10.1016/j.cell.2017.08.009
item.page.type
info:eu-repo/semantics/article
Description
© 2017 Elsevier Inc. This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the accepted version of a published Work that appeared in final form in cell. To access the final edited and published work see https://doi.org/10.1016/j.cell.2017.08.009
Abstract
Expression of many disease-related aggregation-prone proteins results in cytotoxicity and the formation of large intracellular inclusion bodies. To gain insight into the role of inclusions in pathology and the in situ structure of protein aggregates inside cells, we employ advanced cryo-electron tomography methods to analyze the structure of inclusions formed by polyglutamine (polyQ)-expanded huntingtin exon 1 within their intact cellular context. In primary mouse neurons and immortalized human cells, polyQ inclusions consist of amyloid-like fibrils that interact with cellular endomembranes, particularly of the endoplasmic reticulum (ER). Interactions with these fibrils lead to membrane deformation, the local impairment of ER organization, and profound alterations in ER membrane dynamics at the inclusion periphery. These results suggest that aberrant interactions between fibrils and endomembranes contribute to the deleterious cellular effects of protein aggregation.
publication.page.subject
Citation
Cell. Vol. 171, Issue 1, 21 September 2017, Pages 179-187.e10
URI
http://hdl.handle.net/10201/136738
item.page.embargo
Collections
ArtĂ­culos
Ir a EstadĂ­sticas