Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center
Wang, J.; Wu, M.; Magupalli, V.; Dahlberg, P.; Wu, H.; Jensen, G.
Show abstract
The NLRP3 inflammasome is a multi-protein molecular machine that mediates inflammatory responses in innate immunity. Its dysregulation has been linked to a large number of human diseases. Using cryogenic fluorescence-guided focused-ion-beam (cryo-FIB) milling and electron cryo-tomography (cryo-ET), we obtained 3-D images of the NLRP3 inflammasome in situ at various stages of its activation at macromolecular resolution. The cryo-tomograms unexpectedly reveal dense condensates of the human macrophage NLRP3 inflammasome that form within and around the microtubule organizing center (MTOC). We also find that following activation, the trans-Golgi network disperses and 50-nm NLRP3-associated vesicles appear which likely ferry NLRP3 to the MTOC. At later time points after activation, the electron-dense condensates progressively solidify and the cells undergo pyroptosis with widespread damaged mitochondria and autophagasomal structures.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis 96%
- Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways 95%
- Structural basis for surface activation of the classical complement cascade by the short pentraxin C-reactive protein 95%
Similar papers in this journal
- The structure and global distribution of the endoplasmic reticulum network is actively regulated by lysosomes 95%
- Caveolae promote successful abscission by controlling intercellular bridge tension during cytokinesis 95%
- Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome 94%
- Correlative three-dimensional super-resolution and block face electron microscopy of whole vitreously frozen cells 94%
- The nucleus acts as a ruler tailoring cell responses to spatial constraints 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.