| Autor: |
Nadjar, Julien, Monnier, Sylvain, Bastien, Estelle, Huber, Anne-Laure, Oddou, Christiane, Bardoulet, Léa, Leloup, Hubert B., Ichim, Gabriel, Vanbelle, Christophe, Py, Bénédicte F., Destaing, Olivier, Petrilli, Virginie |
| Předmět: |
|
| Zdroj: |
Science Signaling; 4/23/2024, Vol. 17 Issue 833, p1-13, 13p |
| Abstrakt: |
Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck–like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation. We demonstrated that inducing the light-sensitive oligomerization of ASC was sufficient to recapitulate the classical features of inflammasomes within minutes. This system showed that there were two phases of cell swelling during pyroptosis. This approach offers avenues for biophysical investigations into the intricate nature of cellular volume control and plasma membrane rupture during cell death. Editor's summary: Pyroptosis is an inflammation-driven form of programmed cell death that depends on the activation of caspase-1. Assembly of the inflammasome, a multiprotein complex that is activated by various priming signals, is necessary to recruit and activate caspase-1. Nadjar et al. developed an optogenetic method of activating inflammasomes by inducing the oligomerization of the core inflammasome adaptor protein ASC in response to blue light. Clustering of ASC was sufficient to generate an inflammasome response and pyroptotic cell swelling. Thus, this tool may facilitate studies requiring temporal resolution of inflammasome-driven events. —Amy E. Baek [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
