RT Journal Article SR Electronic T1 A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo JF bioRxiv FD Cold Spring Harbor Laboratory SP 079814 DO 10.1101/079814 A1 Maira Arruda Cardoso A1 Marcio Fontenele A1 Bomyi Lim A1 Paulo Mascarello Bisch A1 Stanislav Shvartsman A1 Helena Marcolla Araujo YR 2016 UL http://biorxiv.org/content/early/2016/10/07/079814.abstract AB The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus resulting in a nuclear gradient of the NFκB effector Dorsal. Here we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and Dorsal target genes. Quantitative analysis using a series of loss and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient behave differently respective to Cactus fluctuations. Unexpectedly, Cactus favors Dorsal nuclear localization required as response to high Toll signals at the ventral side of the embryo. Furthermore, N-terminal deleted Cactus mimics these effects, indicating that the ability of Cactus to favor Toll stems from mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that unexplored mechanisms are at play to ensure a correct response to high Toll signals.Summary: The IκB protein Cactus favors high Toll signals, revealing that the ventral and lateral aspects of the Dorsal/NFκB nuclear gradient behave differently respective to Cactus concentrations in the Drosophila embryo.