TY - JOUR
T1 - A novel function for the iκB inhibitor cactus in promoting dorsal nuclear localization and activity in the Drosophila embryo
AU - Cardoso, Maira Arruda
AU - Fontenele, Marcio
AU - Lim, Bomyi
AU - Bisch, Paulo Mascarello
AU - Shvartsman, Stanislav Y.
AU - Araujo, Helena Marcolla
N1 - Publisher Copyright:
© 2017, Company of Biologists Ltd. All rights reserved.
PY - 2017/8/15
Y1 - 2017/8/15
N2 - 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.
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 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.
KW - Cactus
KW - Dorsal-ventral patterning
KW - Drosophila
KW - IκB
KW - NFκB
KW - Toll
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UR - http://www.scopus.com/inward/citedby.url?scp=85027561025&partnerID=8YFLogxK
U2 - 10.1242/dev.145557
DO - 10.1242/dev.145557
M3 - Article
C2 - 28705899
AN - SCOPUS:85027561025
SN - 0950-1991
VL - 144
SP - 2907
EP - 2913
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 16
ER -