Publication: Early endosome autoantigen 1 regulates IL-1β release upon caspase-1 activation independently of gasdermin D membrane permeabilization
Authors
Martín Sánchez, María Rosario Fátima ; Baroja Mazo, Alberto ; Compan, Vince ; Tapia Abellán, Ana ; Coullin, Isabelle ; Pelegrín Vivancos, Pablo
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/s41598-019-42298-4
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info:eu-repo/semantics/article
Description
Abstract
Unconventional protein secretion represents an important process of the inflammatory response.The release of the pro-inflammatory cytokine interleukin (IL)-1β which burst during pyroptosis asa consequence of gasdermin D plasma membrane pore formation, can also occur through otherunconventional secretion pathways dependent on caspase-1 activation. However, how caspase-1mediates cytokine release independently of gasdermin D remains poorly understood. Here weshow that following caspase-1 activation by different inflammasomes, caspase-1 cleaves earlyendosome autoantigen 1 (EEA1) protein at Asp127/132 . Caspase-1 activation also results in the releaseof the endosomal EEA1 protein in a gasdermin D-independent manner. EEA1 knock-down resultsin adecreased release of caspase-1 and IL-1β, but the pyroptotic release of other inflammasomecomponents and lactate dehydrogenase was not affected. This study shows how caspase-1 control therelease of EEA1 and IL-1β in a pyroptotic-independent manner
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Citation
Sci Rep 9, 5788 (2019)
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