A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway

Abstract

The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-kappa B pathway in mammals are homologous signal transduction pathways that mediate several different biological responses. In Drosophila, genetic analysis of dorsal-ventral patterning of the embryo has defined the series of genes that mediate the Toll-Dorsal pathway. Binding of extracellular ligand activates the transmembrane receptor Toll, which requires the novel protein Tube to activate the cytoplasmic serine/threonine kinase Pelle. Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein. Once Cactus is degraded in response to signal, Dorsal is free to move into the nucleus where it regulates transcription of specific target genes. The Toll, tube, pelle, cactus, and dorsal genes also appear to be involved in Drosophila immune response. Because the IL-1R-NF-kappa B pathway plays a role in vertebrate innate immunity and because plant homologues of the Toll-Dorsal pathway are important in plant disease resistance, it is likely that this pathway arose before the divergence of plants and animals as a defense against pathogens.

Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein

“…In contrast to Toll-pathway mutants, homozygous seml females are fertile. Therefore seml does not seem to participate in the Toll-dependent control of dorsoventral axis formation in early embryos 16 . To map the seml mutation, we tested the ability of de®ciencies in the ®rst chromosome to complement the mutant phenotypes.…”

The road to Toll

“…I also made the crucial observation that the level of [71][72][73][74] . The Toll pathway is also used at later developmental stages, including morphogenetic movement, muscle attachment 75 peptides, indicating the selective activation of the Toll pathway 34 . Furthermore, Toll-deficient flies succumb rapidly to B. bassiana infections.…”

How Drosophila combats microbial infection: a model to study innate immunity and host–pathogen interactions

“…The current model is that each AMP-encoding gene is regulated by a balanced activity of two distinct signal transduction pathways: the Toll pathway, which is largely activated by fungal infection and Gram-positive bacteria, and the immune deficiency (Imd) pathway, which is mainly activated by Gram-negative bacteria (Figure 4). Many components of the Toll pathway were previously identified to be mutations that affect embryonic dorsoventral patterning [29]. By contrast, factors that function in the Imd pathway to regulate antibacterial responses remained largely unknown until the past year.…”