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  Proteomics reveals distinct mechanisms regulating the release of cytokines and alarmins during pyroptosis

Phulphagar, K., Kuehn, L. I., Ebner, S., Frauenstein, A., Swietlik, J. J., Rieckmann, J., et al. (2021). Proteomics reveals distinct mechanisms regulating the release of cytokines and alarmins during pyroptosis. Cell Reports, 34(10): 108826. doi:10.1016/j.celrep.2021.108826.

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1-s2.0-S2211124721001406-main.pdf (Publisher version), 5MB
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© 2021 The Author(s).
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Open Access, Under a Creative Commons license
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 Creators:
Phulphagar, Kshiti1, Author           
Kuehn, Lars I.1, Author
Ebner, Stefan1, Author           
Frauenstein, Annika1, Author           
Swietlik, Jonathan J.1, Author           
Rieckmann, Jan1, Author           
Meissner, Felix1, Author           
Affiliations:
1Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: Q EXACTIVE HF; GASDERMIN-D; UNCONVENTIONAL SECRETION; PORE FORMATION; CELL-DEATH; INFLAMMASOME; MEMBRANE; ACTIVATION; INTERLEUKIN-1-BETA; QUANTIFICATIONCell Biology;
 Abstract: A major pathway for proinflammatory protein release by macrophages is inflammasome-mediated pyroptotic cell death. As conventional secretion, unconventional secretion, and cell death are executed simultaneously, however, the cellular mechanisms regulating this complex paracrine program remain incompletely understood. Here, we devise a quantitative proteomics strategy to define the cellular exit route for each protein by pharmacological and genetic dissection of cellular checkpoints regulating protein release. We report the release of hundreds of proteins during pyroptosis, predominantly due to cell lysis. They comprise constitutively expressed and transcriptionally induced proteins derived from the cytoplasm and specific intracellular organelles. Many low-molecular-weight proteins including the cytokine interleukin-1b, alarmins, and lysosomal-cargo proteins exit cells in the absence of cell lysis. Cytokines and alarmins are released in an endoplasmic reticulum (ER)-Golgi-dependent manner as free proteins rather than by extracellular vesicles. Our work provides an experimental framework for the dissection of cellular exit pathways and a resource for pyroptotic protein release.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 20
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 Table of Contents: -
 Rev. Type: -
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Project name : project-IDs 165054336 (SFB 914), 360372040 (SFB 1335), and 408885537 (TRR 274)
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Funding organization : German Research Foundation

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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 34 (10) Sequence Number: 108826 Start / End Page: - Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247