Drosophila tan encodes a novel hydrolase required in pigmentation and vision.
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.
True
John R
JR
Department of Ecology and Evolution, State University of New York, Stony Brook, New York, United States of America. jrtrue@life.bio.sunysb.edu
Yeh
Shu-Dan
SD
Hovemann
Bernhard T
BT
Kemme
Tobias
T
Meinertzhagen
Ian A
IA
Edwards
Tara N
TN
Liou
Shian-Ren
SR
Han
Qian
Q
Li
Jianyong
J
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*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C431070:t protein, Drosophila