A novel function for the I{kappa}B inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo [RESEARCH REPORT]

Maira Arruda Cardoso, Marcio Fontenele, Bomyi Lim, Paulo Mascarello Bisch, Stanislav Y. Shvartsman, and Helena Marcolla Araujo

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 IB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFB effector Dorsal. Here, we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and on 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 can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFB inhibitor, ensuring a correct response to Toll signals.

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