A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.

TitleA novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.
Publication TypeJournal Article
Year of Publication2017
AuthorsCardoso, MArruda, Fontenele, M, Lim, B, Bisch, PMascarello, Shvartsman, SY, Araujo, HMarcolla
JournalDevelopment
Volume144
Issue16
Pagination2907-2913
Date Published2017 08 15
ISSN1477-9129
KeywordsAlleles, Animals, Calpain, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Embryo, Nonmammalian, Nuclear Proteins, Phosphoproteins, Transcription Factors
Abstract

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 ventral-to-dorsal nuclear gradient of the NFκB 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 NFκB inhibitor, ensuring a correct response to Toll signals.

DOI10.1242/dev.145557
Alternate JournalDevelopment
PubMed ID28705899
PubMed Central IDPMC5592809
Grant ListP40 OD018537 / OD / NIH HHS / United States
R01 GM107103 / GM / NIGMS NIH HHS / United States