title: Drosophila tan encodes a novel hydrolase required in pigmentation and vision.
abstract: Many proteins are used repeatedly in development, but usually the function of the protein is similar in the different contexts. Here we report that the classical Drosophila melanogaster locus tan encodes a novel enzyme required for two very different cellular functions: hydrolysis of N-beta-alanyl dopamine (NBAD) to dopamine during cuticular melanization, and hydrolysis of carcinine to histamine in the metabolism of photoreceptor neurotransmitter. We characterized two tan-like P-element insertions that failed to complement classical tan mutations. Both are inserted in the 5' untranslated region of the previously uncharacterized gene CG12120, a putative homolog of fungal isopenicillin-N N-acyltransferase (EC 2.3.1.164). Both P insertions showed abnormally low transcription of the CG12120 mRNA. Ectopic CG12120 expression rescued tan mutant pigmentation phenotypes and caused the production of striking black melanin patterns. Electroretinogram and head histamine assays indicated that CG12120 is required for hydrolysis of carcinine to histamine, which is required for histaminergic neurotransmission. Recombinant CG12120 protein efficiently hydrolyzed both NBAD to dopamine and carcinine to histamine. We conclude that D. melanogaster CG12120 corresponds to tan. This is, to our knowledge, the first molecular genetic characterization of NBAD hydrolase and carcinine hydrolase activity in any organism and is central to the understanding of pigmentation and photoreceptor function.
authors.affiliation: Department of Ecology and Evolution, State University of New York, Stony Brook, New York, United States of America. jrtrue@life.bio.sunysb.edu
authors.forename: John R
authors.initials: JR
authors.lastname: True
authors.forename: Shu-Dan
authors.initials: SD
authors.lastname: Yeh
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Hovemann
authors.forename: Tobias
authors.initials: T
authors.lastname: Kemme
authors.forename: Ian A
authors.initials: IA
authors.lastname: Meinertzhagen
authors.forename: Tara N
authors.initials: TN
authors.lastname: Edwards
authors.forename: Shian-Ren
authors.initials: SR
authors.lastname: Liou
authors.forename: Qian
authors.initials: Q
authors.lastname: Han
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004596:Electroretinography; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D009154:Mutation; D010858:Pigmentation / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014785:Vision, Ocular / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C431070:t protein, Drosophila