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https://doi.org/10.1016/j.cell.2017.12.030
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Título: | In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment |
Fecha de publicación: | 8-feb-2018 |
Editorial: | Elsevier |
Cita bibliográfica: | Cell. Vol. 172, Issue 4, 8 February 2018, Pages 696-705.e12 |
ISSN: | Print: 0092-8674 Electronic: 1097-4172 |
Palabras clave: | ALS FTD Dipeptide-repeat proteins UPS Cryo-EM Cryo-ET Cryo-FIB Cryoelectron microscopy |
Resumen: | Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo-electron tomography to dissect the molecular architecture of protein aggregates within intact neurons at high resolution. We focus on the poly-Gly-Ala (poly-GA) aggregates resulting from aberrant translation of an expanded GGGGCC repeat in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. We find that poly-GA aggregates consist of densely packed twisted ribbons that recruit numerous 26S proteasome complexes, while other macromolecules are largely excluded. Proximity to poly-GA ribbons stabilizes a transient substrate-processing conformation of the 26S proteasome, suggesting stalled degradation. Thus, poly-GA aggregates may compromise neuronal proteostasis by driving the accumulation and functional impairment of a large fraction of cellular proteasomes. |
Autor/es principal/es: | Guo, Qiang Lehmer, Carina Martinez-Sanchez, Antonio Rudack, Till Beck, Florian Hartmann, Hannelore Pérez-Berlanga, Manuela Frédéric, Frottin Hipp, Mark Hartl, Ulrich Edbauer, Dieter Baumeister, Wolfgang Fernández-Busnadiego, Rubén |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Economía Financiera y Contabilidad |
Versión del editor: | https://www.sciencedirect.com/science/article/pii/S0092867417315106?via%3Dihub |
URI: | http://hdl.handle.net/10201/136775 |
DOI: | https://doi.org/10.1016/j.cell.2017.12.030 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 22 |
Derechos: | info:eu-repo/semantics/openAccess |
Descripción: | © 2018. 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.2017.12.030 |
Aparece en las colecciones: | Artículos: Ingeniería de la Información y las Comunicaciones |
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