Dataset Information

A Membrane Potential- and Calpain-Dependent Reversal of Caspase-1 Inhibition Regulates Canonical NLRP3 Inflammasome.

ABSTRACT: The NLRP3 inflammasome senses a range of cellular disturbances, although no consensus exists regarding a common mechanism. Canonical NLRP3 activation is blocked by high extracellular K+, regardless of the activating signal. We report here that canonical NLRP3 activation leads to Ca2+ flux and increased calpain activity. Activated calpain releases a pool of Caspase-1 sequestered by the cytoskeleton to regulate NLRP3 activation. Using electrophysiological recording, we found that resting-state eukaryotic membrane potential (MP) is required for this calpain activity, and depolarization by high extracellular K+ or artificial hyperpolarization results in the inhibition of calpain. Therefore, the MP/Ca2+/calpain/Caspase-1 axis acts as an independent regulatory mechanism for NLRP3 activity. This finding provides mechanistic insight into high K+-mediated inhibition of NLRP3 activation, and it offers an alternative model of NLRP3 inflammasome activation that does not involve K+ efflux.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6201321 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A Membrane Potential- and Calpain-Dependent Reversal of Caspase-1 Inhibition Regulates Canonical NLRP3 Inflammasome.

Zhang Yifei Y Rong Hua H Zhang Fang-Xiong FX Wu Kun K Mu Libing L Meng Junchen J Xiao Bailong B Zamponi Gerald W GW Shi Yan Y

Cell reports 20180801 9

The NLRP3 inflammasome senses a range of cellular disturbances, although no consensus exists regarding a common mechanism. Canonical NLRP3 activation is blocked by high extracellular K<sup>+</sup>, regardless of the activating signal. We report here that canonical NLRP3 activation leads to Ca<sup>2+</sup> flux and increased calpain activity. Activated calpain releases a pool of Caspase-1 sequestered by the cytoskeleton to regulate NLRP3 activation. Using electrophysiological recording, we found ...[more]

PMID: 30157429

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Dataset Information

A Membrane Potential- and Calpain-Dependent Reversal of Caspase-1 Inhibition Regulates Canonical NLRP3 Inflammasome.

Publications

A Membrane Potential- and Calpain-Dependent Reversal of Caspase-1 Inhibition Regulates Canonical NLRP3 Inflammasome.

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