IRE-1 requires its nuclease activity independently of canonical UPR pathways.

<p>A–B. Fluorescent micrographs of mutant animals with tracings (right panels) of the genotypes indicated. Anterior is to the left and ventral down in all images. Arrowheads indicate the PVD axons and scale bars 20 μm. C. Quantification of animals with PVD defects in animals of the indicated genotypes. D. Structure function analyses of <i>ire-1(ok799)</i> mutant animals with the constructs as indicated. All constructs were transgenically expressed under control of the heterologous pan-neuronal <i>Prgef-1</i> promoter. Transgenic (T) and non-transgenic siblings (NT) were analyzed in parallel in different transgenic lines (L1, L2, etc.). tm: transmembrane domain. E. <i>xbp-1</i> splicing assay using RNA from the genotypes indicated (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006579#sec008" target="_blank">Materials and Methods</a> for details). Successful splicing is evidenced by the presence of a band that is slightly smaller (237 nt) than the unspliced band (260 nt), both indicated by black arrowheads. The size of selected bands in a molecular marker is shown. F. Quantification of animals with PVD defects in animals of the indicated genotypes.