The unfolded protein response element IRE1? senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling.

ABSTRACT: The plasma membrane and all membrane-bound organelles except for the Golgi and endoplasmic reticulum (ER) are equipped with pattern-recognition molecules to sense microbes or their products and induce innate immunity for host defense. Here, we report that inositol-requiring-1? (IRE1?), an ER protein that signals in the unfolded protein response (UPR), is activated to induce inflammation by binding a portion of cholera toxin as it co-opts the ER to cause disease. Other known UPR transducers, including the IRE1?-dependent transcription factor XBP1, are dispensable for this signaling. The inflammatory response depends instead on the RNase activity of IRE1? to degrade endogenous mRNA, a process termed regulated IRE1?-dependent decay (RIDD) of mRNA. The mRNA fragments produced engage retinoic-acid inducible gene 1 (RIG-I), a cytosolic sensor of RNA viruses, to activate NF-?B and interferon pathways. We propose IRE1? provides for a generalized mechanism of innate immune surveillance originating within the ER lumen.

SUBMITTER: Cho JA 

PROVIDER: S-EPMC3766372 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature