A reaction-diffusion network model predicts a dual role of Cactus/IκB to regulate Dorsal/NFκB nuclear translocation in Drosophila
Fig 1
Mathematical modeling of nuclear Dorsal gradient in Drosophila embryos.
(A) Schematic representation of the Reaction-Diffusion Network Model regulating nuclear Dorsal (nDl) localization. Kinetic constants k1 and k2 mediate synthesis and Toll-independent degradation of the inhibitor Cactus, respectively. Dl dimers can enter and leave the nucleus by direct flow (k3 and k4), independent of Toll activation. k5 and k6 mediate reversible binding between cytoplasmic Dl dimers (cDl0) and free Cactus (Cf) to form trimeric complexes (DlC). DlCT complex is reversibly formed by the interaction between DlC and activated Toll (T) membrane receptor (k7 and k8). Following DlCT complex formation, Toll activation induces Dl and Cactus phosphorylation, releasing Dl and C from the complex. This irreversible reaction is controlled by k9. Cytoplasmic phosphorylated Dl dimers (cDl*) enter the nucleus (nDl*) while phosphorylated and ubiquitinated Cactus (Cub) is degraded by the proteasome (k10). k12 controls nDl* output from the nucleus. Note that T represents only the activated form of the Toll receptor. (B) Detailed reaction network stoichiometry. (C) Key relationships among model species. Total Cactus (C) is the sum of all species that contain Cactus. Total nuclear Dorsal (nDl) is the sum of nDl0 and nDl*. Total cytoplasmic Dorsal (cDl) includes free cDl, cDl*, plus the two DlC and DlCT complexes. Total Dorsal is the sum of nDl and cDl. The model was solved for cleavage cycle 14 embryos.