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research article

Nanoscale organization of the endogenous ASC speck

Glueck, Ivo M.
•
Mathias, Grusha Primal
•
Strauss, Sebastian
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November 16, 2023
Iscience

The NLRP3 inflammasome is a central component of the innate immune system. Its activation leads to for-mation of the ASC speck, a supramolecular assembly of the inflammasome adaptor protein ASC. Different models, based on ASC overexpression, have been proposed for the structure of the ASC speck. Using dual-color 3D super-resolution imaging (dSTORM and DNA-PAINT), we visualized the ASC speck structure following NLRP3 inflammasome activation using endogenous ASC expression. A complete structure was only obtainable by labeling with both anti-ASC antibodies and nanobodies. The complex varies in diameter between similar to 800 and 1000 nm, and is composed of a dense core with emerging filaments. Dual-color confocal fluorescence microscopy indicated that the ASC speck does not colocalize with the microtubule-organizing center at late time points after Nigericin stimulation. From super-resolution images of whole cells, the ASC specks were sorted into a pseudo-time sequence indicating that they become denser but not larger during formation.

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Type
research article
DOI
10.1016/j.isci.2023.108382
Web of Science ID

WOS:001115069800001

Author(s)
Glueck, Ivo M.
•
Mathias, Grusha Primal
•
Strauss, Sebastian
•
Rat, Virgile
•
Gialdini, Irene
•
Ebert, Thomas Sebastian
•
Stafford, Che
•
Agam, Ganesh
•
Manley, Suliana  
•
Hornung, Veit
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Date Issued

2023-11-16

Publisher

Cell Press

Published in
Iscience
Volume

26

Issue

12

Article Number

108382

Subjects

Nlrp3 Inflammasome Activation

•

Recruitment Domain Protein

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Nf-Kappa-B

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Superresolution Microscopy

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Human Monocytes

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Pyrin Domain

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Adapter Asc

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Cell-Death

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Binding

•

Redistribution

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LEB  
FunderGrant Number

Studienstiftung des Deutschen Volkes for a PhD fellowship

Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

201269156

Ludwig -Maximilian University of Munich via the Center for NanoScience (CeNS)

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Available on Infoscience
February 20, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/204512
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