The metabolism of histamine in theDrosophilaoptic lobe involves an ommatidial pathway: β-alanine recycles through the retina

Abstract

SUMMARYFlies recycle the photoreceptor neurotransmitter histamine by conjugating it to -alanine to form -alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and -alanine. In Drosophila, -alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected -alanine is present throughout the flyʼs entire brain, and is enhanced in the retina especially in the pseudocone, pigment and photoreceptor cells of the ommatidia. HPLC determinations reveal 10.7ng of -alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head -alanine increases more than after drinking L-aspartic acid, indicating the effectiveness of the uracil pathway. Mutants of black, which lack aspartate decarboxylase, cannot synthesize -alanine from L-aspartate but can still synthesize it efficiently from uracil. Our findings demonstrate a novel function for pigment cells, which not only screen ommatidia from stray light but also store and transport -alanine and carcinine. This role is consistent with a -alanine-dependent histamine recycling pathway occurring not only in the photoreceptor terminals in the lamina neuropile, where carcinine occurs in marginal glia, but vertically via a long pathway that involves the retina. The laminaʼs marginal glia are also a hub involved in the storage and/or disposal of carcinine and -alanine.

Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila

“…Previous work has shown that carcinine and β-alanine are present in both the retina and lamina (20). By immunostaining, we confirmed the presence of all three molecules (i.e., histamine, carcinine, and β-alanine) in the retina of wild-type flies ( Fig.…”

“…Any histamine/carcinine/β-alanine signal detected within the staining region of ATPα would be in pigment cells, whereas signals on the border or outside of the ATPα staining region are considered to be in photoreceptors. The results indicated that β-alanine was more highly present in pigment cells than in photoreceptors, which is consistent with a previous report (20). Importantly, both pigment cells and photoreceptors contained carcinine and histamine ( To test whether the presence of histamine, carcinine, and β-alanine in pigment cells is relevant to the recycling of histamine, we costained these molecules with ATPα in the retina of ebony 1 and tan 1 mutants (Fig.…”

“…Third, compared with the axon, the cell body of photoreceptor contains a larger amount of Tan protein (36) and thus could be the major site of histamine regeneration. Fourth, β-alanine is concentrated in pigment cells (20). This pool of β-alanine is further increased when Ebony activity is impaired and thus may represent a major source of β-alanine for carcinine synthesis.…”

Genetic basis of natural variation in body pigmentation inDrosophila melanogaster

“…It can be formed from aspartate by aspartate decarboxylase (encoded by black) or from uracil by dihydropyrimidine dehydrogenase (Pyd1, encoded by su(r)), dihydropyrimidase (Pyd2), and b-ureidopropionase (Pyd3). 31 This supports our previous findings that genetic variation at a number of steps in biosynthetic, regulatory, and developmental pathways may contribute to natural variation in abdominal pigmentation.…”

Pigmentation and behavior: potential association through pleiotropic genes in <i>Drosophila</i>

“…Some inconsistent views exist about whether the majority of the black melanin is produced from dopa or dopamine (pathways indicated by red broken arrows). (B) Pathways for histamine recycling in the visual system; redrawn from Borycz et al (2002Borycz et al ( , 2012, True et al (2005) and Gavin et al (2007). Core enzymes in the pathways are indicated in blue.…”