Drosophila and E. coli Share a Strategy for Signal Release

The Faculty of 1000 is aWeb-based literature awareness tool published by BioMed Central. For more information visit www.facultyof1000.com. Science sometimes progresses by persistence and attention to detail. This was the case for the recent discovery that a bacterium and the fruit fly apparently share a strategy for signal release, despite one being a prokaryote and the other a eukaryote.1 The new view suggests that quorum sensing in bacteria and signal transduction in multicellular organisms may represent a continuum in communication skills. "This paper is really the first demonstration that some aspects of extracellular signaling in multicellular organisms are conserved in bacteria," wrote Ralph Isberg, professor of molecular biology and microbiology at Tufts University School of Medicine, who reviewed the paper for the Faculty of 1000. Graduate student Marco Gallio catalyzed the research collaboration that revealed the signaling connection. "In late 1998, Marco became interested in one of the classic fly mutations [roughoid] which was first described in 1920," recalls Gallio's mentor Per Kylsten, senior lecturer in developmental biology at Sodertorns Hogskola, Huddinge, Sweden. Gallio set about cloning the gene, but Matthew Freeman, group leader at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, beat him to it, placing roughoid in the protein family Rhomboid.2 But Gallio wanted to know more, particularly about the protein's function. "I compared rhomboid-related sequences to identify any stretch that would suggest a catalytic site," he recalls. "I found a conserved motif that turned out to be the serine protease catalytic site. Having found so many related sequences, it seemed obvious to determine if any had a defined function, in order to learn what Rhomboid could be doing biochemically. This is how I found AarA," the bacterial protein.3 The AarA connection led him to Philip Rather and his group at Case Western Reserve University, who identified the aarA gene in Providencia stuartii in 1994. "When we originally cloned the aarA gene, we noted that the AarA protein displayed similarity to Rhomboid and also the Escherichia coli protein GlpG," says Rather, an associate professor of molecular biology and microbiology. "However, the function of both Rhomboid and GlpG were unknown at that time." The connection between aarA and quorum sensing was established in 1999.4 Gallio proposed collaborating with Rather, and the rest, it appears, will make history. The current paper describes the work showing that Rhomboid and AarA can swap roles in the organisms of origin. "The Rhomboid protein from the bacterium P. stuartii, AarA, can trigger EGF [epidermal growth factor] receptor signaling in Drosophila in a similar manner to its Drosophila counterpart," wrote Freeman, another Faculty of 1000 reviewer. "Conversely, Drosophila Rhomboid-1 can rescue a quorum sensing defect in aarA mutant Providencia." The evolutionary implications of the findings are profound. "Signaling systems that rely on precursor proteins that are cleaved into active signals are found in bacteria, yeasts, plants, and animals," Gallio says. "Our results suggest that RHO-mediated intramembranous cleavage could be an ancient mechanism for extracellular signal release." So far, researchers have more details for the fruit fly than the bacterium. In Drosophila, Rhomboid cleaves another membrane protein, Spitz, which releases a soluble ligand for the EGF receptor. "Rhomboids release membrane-bound signaling peptides or proteins from a signaling cell to its neighbors," explains Kylsten. In the bacteria, AarA protein cleaves an unknown substrate, releasing a soluble peptide-like signal. But what happens after the signal is sent differs in these organisms, reflecting the evolutionary constraints of eukaryotic versus prokaryotic life. In the fruit fly, ligand binding to the EGF receptor directs development at different stages, including establishing egg polarity, guiding ectoderm specialization, and controlling development of the eye, wing venation, and the excretory system. Whereas vertebrates have several genes that encode both the EGF receptor and multiple ligands, invertebrates have only one gene encoding the EGF receptor and several ligands. In the bacteria, AarA is part of a quorum sensing system that lets microorganisms detect the concentration of signaling molecules in the immediate environment, and then use this information to assess cell density. When enough bacteria accumulate, certain activities become possible, such as bioluminescence, biofilm formation, and increased virulence. For quorum sensing bacteria, the whole is, in a sense, greater than the sum of the parts. The quorum sensing system of bacteria and the signal transduction mechanism seen in multicellular organisms may signify a continuum in communication skills. Says Gallio: "Bacterial quorum sensing could be the little world's correspondent of the many signals that regulate growth and patterning of animal tissues. If cell signaling of this kind was already active in the cells that evolved to become the first multicellular organism, it must have been instrumental to the completion of this dramatic step in evolution." Ricki Lewis (rickilewis@nasw.org) is a contributing editor. References 1. M. Gallio et al., "A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes," Proceedings of the National Academy of Sciences, 99:12208-13, Sept. 17, 2002. 2. J.D. Wasserman et al., "A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to act on EGF receptor signaling," Genes & Development, 14:1651-63, 2000. 3. M. Gallio, P. Kylsten, "Providencia may help find a function for a novel, widespread protein family," Current Biology, 19:R693-4, 2000. 4. P.N. Rather et al., "Providencia stuartii genes activated by cell-to-cell signaling and identification of a gene required for production or activity of an extracellular factor," Journal of Bacteriology, 181:7185-91, 1999.

Drosophila and E. coli Share a Strategy for Signal Release

Interested in reading more?

Become a Member of