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  In Situ Architecture and Cellular Interactions of PolyQ Inclusions

Bäuerlein, F. J. B., Saha, I., Mishra, A., Kalemanov, M., Martinez-Sanchez, A., Klein, R., et al. (2017). In Situ Architecture and Cellular Interactions of PolyQ Inclusions. Cell, 171(1), 179-187. doi:10.1016/j.cell.2017.08.009.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-E642-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-E643-1
Genre: Journal Article

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 Creators:
Bäuerlein, Felix J. B.1, Author              
Saha, Itika2, Author              
Mishra, Archana3, Author              
Kalemanov, Maria1, Author              
Martinez-Sanchez, Antonio1, Author              
Klein, Rüdiger3, Author              
Dudanova, Irina3, Author              
Hipp, Mark S.2, Author              
Hartl, F. Ulrich2, Author              
Baumeister, Wolfgang1, Author              
Fernandez-Busnadiego, Ruben1, Author              
Affiliations:
1Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              
2Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              
3Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              

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Free keywords: cryo-electron tomography, cryo-EM, cryo-focused ion beam milling, protein aggregation, inclusion body, polyglutamine expansion, amyloid fibril, membrane disruption, endoplasmic reticulum
 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.

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 Dates: 2017-06-302017-03-312017-08-072017-09-07
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.cell.2017.08.009
 Degree: -

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 171 (1) Sequence Number: - Start / End Page: 179 - 187 Identifier: ISSN: 0092-8674
CoNE: /journals/resource/954925463183