Fig. 1. Regulation and detection of the IRE1/XBP1 pathway. (A) A schematic diagram of the IRE1/XBP1 pathway in Drosophila. IRE1 is an ER stress sensor that directly binds to misfolded peptides in the ER lumen. Upon detecting ER stress, IRE1 activates its RNase domain on the cytoplasmic side. IRE1 works together with a tRNA ligase to catalyze the splicing of XBP1 mRNA. The product of this spliced isoform acts as a transcription factor that induces ER quality control genes. In addition, IRE1 promotes the decay of many mRNAs associated with the ER. (B) The XBP1-GFP reporter used to detect IRE1 activity in vivo. As XBP1 mRNA splicing by IRE1 shifts the reading frame, an XBP1-GFP fusion transgene was designed to have GFP expressed in frame only when IRE1-mediated splicing occurs.