Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization

Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization

Blog Article

Abstract NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation.Aberrant activity of NLRP3 occurs in many human diseases.NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum.

Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis.Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated nightstick twm-850xl cells.The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain.

Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation.Mitochondria are not associated kicker pro comp 10 with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization.