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Drosophila tan encodes a novel hydrolase required in pigmentation and vision.

True JR, Yeh SD, Hovemann BT, Kemme T, Meinertzhagen IA, Edwards TN, Liou SR, Han Q, Li J - PLoS Genet. (2005)

Bottom Line: We characterized two tan-like P-element insertions that failed to complement classical tan mutations.Both P insertions showed abnormally low transcription of the CG12120 mRNA.We conclude that D. melanogaster CG12120 corresponds to tan.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, State University of New York, Stony Brook, New York, United States of America. jrtrue@life.bio.sunysb.edu

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.

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Tan Functions in Diverse Developmental and Metabolic Pathways(A) In developing adult epidermal cells, Tan catalyzes the production of dopamine from NBAD during pigment development. This is one of four parallel pathways by which dopa or dopamine derivatives are secreted into the developing cuticle as precursors for distinct pigments. aaNAT, arylalkylamine-N-acetyl transferase; DDC, dopa decarboxylase; NADA, N-acetyl dopamine; PO, phenol oxidase; TH, tyrosine hydroxylase.(B) In the photoreceptor, Tan catalyzes the hydrolysis of N-β-alanyl histamine (carcinine) to histamine for re-uptake by the presynaptic photoreceptor cell (R). CA, carcinine; EG, epithelial glial cell; HA, histamine.
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pgen-0010063-g005: Tan Functions in Diverse Developmental and Metabolic Pathways(A) In developing adult epidermal cells, Tan catalyzes the production of dopamine from NBAD during pigment development. This is one of four parallel pathways by which dopa or dopamine derivatives are secreted into the developing cuticle as precursors for distinct pigments. aaNAT, arylalkylamine-N-acetyl transferase; DDC, dopa decarboxylase; NADA, N-acetyl dopamine; PO, phenol oxidase; TH, tyrosine hydroxylase.(B) In the photoreceptor, Tan catalyzes the hydrolysis of N-β-alanyl histamine (carcinine) to histamine for re-uptake by the presynaptic photoreceptor cell (R). CA, carcinine; EG, epithelial glial cell; HA, histamine.

Mentions: The molecular identification of tan helps clarify a crucial step in dopamine metabolism and melanin biosynthesis in epidermal cells. All developing adult epidermal cells in insects are capable of secreting catecholamine precursors of melanin and sclerotin, and current models [1,6,24] propose that the patterns of adult melanin reflect the differential spatial regulation of four parallel branches from the core dopamine pathway catalyzed by tyrosine hydroxylase and dopa decarboxylase (Figure 5A). One of the four branches produces dopa melanin, which is under the control of yellow [6,25], the exact function of which is unknown, and at least two Yellow-related proteins, Yellow-f and Yellow-f2, which convert dopachrome to 5,6-dihydroxyindole [26]. Dopamine is also secreted and converted into dopamine melanin through an as yet uncharacterized pathway. Areas of the cuticle that are not melanized secrete NBAD, produced by the action of the Ebony protein [2,6], resulting in yellow or light tan cuticle, or N-acetyl dopamine, produced by the action of the arylalkylamine N-acyltransferases [27], which results in transparent cuticle (J. R. T., unpublished data). All of these precursors are extracellularly polymerized and crosslinked to cuticle proteins, probably through the action of a common set of enzymes, including phenol oxidases [28], the functions of which in the developing cuticle are not well characterized. Tyrosine and catecholamines are also provided to some degree from the hemolymph [1,29], and a hemolymph supply of melanin precursors is required for wing pigmentation [24].


Drosophila tan encodes a novel hydrolase required in pigmentation and vision.

True JR, Yeh SD, Hovemann BT, Kemme T, Meinertzhagen IA, Edwards TN, Liou SR, Han Q, Li J - PLoS Genet. (2005)

Tan Functions in Diverse Developmental and Metabolic Pathways(A) In developing adult epidermal cells, Tan catalyzes the production of dopamine from NBAD during pigment development. This is one of four parallel pathways by which dopa or dopamine derivatives are secreted into the developing cuticle as precursors for distinct pigments. aaNAT, arylalkylamine-N-acetyl transferase; DDC, dopa decarboxylase; NADA, N-acetyl dopamine; PO, phenol oxidase; TH, tyrosine hydroxylase.(B) In the photoreceptor, Tan catalyzes the hydrolysis of N-β-alanyl histamine (carcinine) to histamine for re-uptake by the presynaptic photoreceptor cell (R). CA, carcinine; EG, epithelial glial cell; HA, histamine.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1285064&req=5

pgen-0010063-g005: Tan Functions in Diverse Developmental and Metabolic Pathways(A) In developing adult epidermal cells, Tan catalyzes the production of dopamine from NBAD during pigment development. This is one of four parallel pathways by which dopa or dopamine derivatives are secreted into the developing cuticle as precursors for distinct pigments. aaNAT, arylalkylamine-N-acetyl transferase; DDC, dopa decarboxylase; NADA, N-acetyl dopamine; PO, phenol oxidase; TH, tyrosine hydroxylase.(B) In the photoreceptor, Tan catalyzes the hydrolysis of N-β-alanyl histamine (carcinine) to histamine for re-uptake by the presynaptic photoreceptor cell (R). CA, carcinine; EG, epithelial glial cell; HA, histamine.
Mentions: The molecular identification of tan helps clarify a crucial step in dopamine metabolism and melanin biosynthesis in epidermal cells. All developing adult epidermal cells in insects are capable of secreting catecholamine precursors of melanin and sclerotin, and current models [1,6,24] propose that the patterns of adult melanin reflect the differential spatial regulation of four parallel branches from the core dopamine pathway catalyzed by tyrosine hydroxylase and dopa decarboxylase (Figure 5A). One of the four branches produces dopa melanin, which is under the control of yellow [6,25], the exact function of which is unknown, and at least two Yellow-related proteins, Yellow-f and Yellow-f2, which convert dopachrome to 5,6-dihydroxyindole [26]. Dopamine is also secreted and converted into dopamine melanin through an as yet uncharacterized pathway. Areas of the cuticle that are not melanized secrete NBAD, produced by the action of the Ebony protein [2,6], resulting in yellow or light tan cuticle, or N-acetyl dopamine, produced by the action of the arylalkylamine N-acyltransferases [27], which results in transparent cuticle (J. R. T., unpublished data). All of these precursors are extracellularly polymerized and crosslinked to cuticle proteins, probably through the action of a common set of enzymes, including phenol oxidases [28], the functions of which in the developing cuticle are not well characterized. Tyrosine and catecholamines are also provided to some degree from the hemolymph [1,29], and a hemolymph supply of melanin precursors is required for wing pigmentation [24].

Bottom Line: We characterized two tan-like P-element insertions that failed to complement classical tan mutations.Both P insertions showed abnormally low transcription of the CG12120 mRNA.We conclude that D. melanogaster CG12120 corresponds to tan.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, State University of New York, Stony Brook, New York, United States of America. jrtrue@life.bio.sunysb.edu

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.

Show MeSH
Related in: MedlinePlus