Nanoscale organization of the endogenous ASC speck.

Autor: Glück IM; Department of Chemistry, Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany.; Center for Nano Science (CENS), Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany., Mathias GP; Department of Chemistry, Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany., Strauss S; Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, Munich, Germany.; Max Planck Institute of Biochemistry, Martinsried, Germany., Rat V; Department of Chemistry, Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany.; Center for Nano Science (CENS), Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany., Gialdini I; Department of Chemistry, Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany.; Center for Nano Science (CENS), Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany., Ebert TS; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität, Munich, Germany., Stafford C; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität, Munich, Germany., Agam G; Department of Chemistry, Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany.; Center for Nano Science (CENS), Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany., Manley S; Laboratory of Experimental Biophysics, École Polytechnique Fédérale de Lausanne, BSP 427 (Cubotron UNIL), Rte de la Sorge, CH-1015 Lausanne, Switzerland., Hornung V; Max Planck Institute of Biochemistry, Martinsried, Germany.; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität, Munich, Germany., Jungmann R; Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, Munich, Germany.; Max Planck Institute of Biochemistry, Martinsried, Germany., Sieben C; Laboratory of Experimental Biophysics, École Polytechnique Fédérale de Lausanne, BSP 427 (Cubotron UNIL), Rte de la Sorge, CH-1015 Lausanne, Switzerland., Lamb DC; Department of Chemistry, Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany.; Center for Nano Science (CENS), Ludwig Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany.
Jazyk: angličtina
Zdroj: IScience [iScience] 2023 Nov 02; Vol. 26 (12), pp. 108382. Date of Electronic Publication: 2023 Nov 02 (Print Publication: 2023).
DOI: 10.1016/j.isci.2023.108382
Abstrakt: The NLRP3 inflammasome is a central component of the innate immune system. Its activation leads to formation 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 ∼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.
Competing Interests: The authors declare no conflict of interest.
(© 2023 The Authors.)
Databáze: MEDLINE