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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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 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: 2017-09-07
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.cell.2017.08.009
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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: https://pure.mpg.de/cone/journals/resource/954925463183