The trace biogenic amine tyramine is present in the nervous systems of animals ranging in complexity from nematodes to mammals. Tyramine is synthesized from tyrosine by the enzyme tyrosine decarboxylase (TDC), a member of the aromatic amino acid family, but this enzyme has not been identified in Drosophila or in higher animals. To further clarify the roles of tyramine and its metabolite octopamine, we have cloned two TDC genes from Drosophila melanogaster, dTdc1 and dTdc2. Although both gene products have TDC activity in vivo, dTdc1 is expressed nonneurally, whereas dTdc2 is expressed neurally. Flies with a mutation in dTdc2 lack neural tyramine and octopamine and are female sterile due to egg retention. Although other Drosophila mutants that lack octopamine retain eggs completely within the ovaries, dTdc2 mutants release eggs into the oviducts but are unable to deposit them. This specific sterility phenotype can be partially rescued by driving the expression of dTdc2 in a dTdc2-specific pattern, whereas driving the expression of dTdc1 in the same pattern results in a complete rescue. The disparity in rescue efficiencies between the ectopically expressed Tdc genes may reflect the differential activities of these gene products. The egg retention phenotype of the dTdc2 mutant and the phenotypes associated with ectopic dTdc expression contribute to a model in which octopamine and tyramine have distinct and separable neural activities.Tyramine, octopamine, and other "trace" biogenic amines are found in most organisms, including bacteria, fungi, and plants, and in animals ranging in complexity from nematodes to mammals. Despite their wide distribution, the biological roles of trace amines are poorly understood. In vertebrates, trace amines are present in low levels and can displace classical biogenic amines from their stores and stimulate outward neurotransmitter efflux from biogenic amine transporters (1). Although there are currently no data to suggest that there are dedicated synapses for trace amines in the brain, the recent discovery of G-protein-coupled receptors that are selectively Additionally, tyramine affects chloride permeability in the Drosophila Malpighian tubule (7), relaxation of muscle tone in the locust oviduct (8), and behavioral responses to cocaine in Drosophila (9).Octopamine in invertebrates is often considered to be the functional homolog of vertebrate norepinephrine and is involved in a diverse range of physiological processes (reviewed in Ref. 10), including Drosophila female fertility. Flies that lack a functional octopamine receptor or cannot synthesize octopamine due to a null allele of tyramine ␤-hydroxylase (T␤h) 2 show a complete egg retention phenotype (11-13). The sterility of T␤h null females is due to a defect in ovulation, which can be rescued by octopamine feeding or by driving the ectopic expression of a T␤h transgene in several driver lines that show overlapping expression in the thoracic tip of the CNS (12, 13).The first step in octopamine biosynthesis is catalyzed by tyrosine...

The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli, a process that results from a translesion synthesis mechanism. The UmuD protein is activated for its role in mutagenesis by a RecA-facilitated autodigestion that removes the N-terminal 24 amino acids. A previous genetic screen for nonmutable umuDmutants had resulted in the isolation of a set of missense mutants that produced UmuD proteins that were deficient in RecA-mediated cleavage (J. R. Battista, T. Ohta, T. Nohmi, W. Sun, and G. C. Walker, Proc. Natl. Acad. Sci. USA 87:7190–7194, 1990). To identify elements of the UmuD′ protein necessary for its role in translesion synthesis, we began with umuD′, a modified form of theumuD gene that directly encodes the UmuD′ protein, and obtained missense umuD′ mutants deficient in UV and methyl methanesulfonate mutagenesis. The D39G, L40R, and T51I mutations affect residues located at the UmuD′2 homodimer interface and interfere with homodimer formation in vivo. The D75A mutation affects a highly conserved residue located at one end of the central strand in a three-stranded β-sheet and appears to interfere with UmuD′2 homodimer formation indirectly by affecting the structure of the UmuD′ monomer. When expressed from a multicopy plasmid, the L40R umuD′ mutant gene exhibited a dominant negative effect on a chromosomal umuD + gene with respect to UV mutagenesis, suggesting that the mutation has an effect on UmuD′ function that goes beyond its impairment of homodimer formation. The G129D mutation affects a highly conserved residue that lies at the end of the long C-terminal β-strand and results in a mutant UmuD′ protein that exhibits a strongly dominant negative effect on UV mutagenesis in a umuD +strain. The A30V and E35K mutations alter residues in the N-terminal arms of the UmuD′2 homodimer, which are mobile in solution.