Meinertzhagen, Ian A.
Permanent URI for this collectionhttps://hdl.handle.net/10222/15737
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Item Open Access Drosophila ABC transporter mutants white, brown and scarlet have altered contents and distribution of biogenic amines in the brain(2008-11) Borycz, J.; Borycz, J. A.; Kubow, A.; Lloyd, V.; Meinertzhagen, I. A.Monoamines such as dopamine, histamine and serotonin (5-HT) are widely distributed throughout the brain of the fruit fly Drosophila melanogaster, where many of their actions have been investigated. For example, histamine is released from photoreceptor synapses in the lamina neuropile of the visual system. Mutations of the genes white, an important eye pigmentation marker in fly genetics that encodes an ABC transporter, and its binding partner brown, cause neural phenotypes not readily reconciled solely with actions in eye pigmentation. We find that flies mutant for these genes, and another binding partner, scarlet, have about half the wild-type amount of histamine in the head, as well as reduced 5-HT and dopamine. These differences parallel reductions in immunoreactivity to the corresponding biogenic amines. They also correlate with the amine content of fractions after differential centrifugation of head homogenates. Thus, most of the amine is found in the vesicle-rich fraction of wild-type head homogenates, whereas it is found in the supernatant fractions from white, brown and scarlet flies. White co-expresses in lamina epithelial glia with Ebony, which conjugates histamine to beta-alanine. Histamine is then released when the conjugate is hydrolyzed in photoreceptors, by Tan. Mutant white ameliorates the effects of tan on head histamine whereas it exacerbates the effects of ebony. Our results are consistent with the proposal that histamine uptake by the epithelial glia may be white dependent. Behavioral abnormalities in white, brown and scarlet mutants could arise because aminergic neurons in the Drosophila brain have reduced amine for release.Item Open Access The metabolism of histamine in the Drosophila optic lobe involves an ommatidial pathway: beta-alanine recycles through the retina(2012-04) Borycz, J.; Borycz, J. A.; Edwards, T. N.; Boulianne, G. L.; Meinertzhagen, I. A.Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to beta-alanine to form beta-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and beta-alanine. In Drosophila, beta-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected beta-alanine is present throughout the fly's 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 beta-alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head beta-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 beta-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 beta-alanine and carcinine. This role is consistent with a beta-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 lamina's marginal glia are also a hub involved in the storage and/or disposal of carcinine and beta-alanine.