Genetic and molecular identification of a Drosophila histidine decarboxylase gene required in photoreceptor transmitter synthesis.

Burg, Martin G.; Sarthy, P. Vijay; Koliantz, Gregore; Pak, William L.

doi:10.1002/j.1460-2075.1993.tb05732.x

Cited by 118 publications

(137 citation statements)

References 47 publications

(50 reference statements)

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“…Further, histidine decarboxylase activity has been demonstrated in Drosophila photoreceptors, suggesting that histamine is synthesized in these cells (2). Drosophila mutants that are deficient in the hdc gene coding for histamine decarboxylase have been identified (4), and flies homozygous for the null mutation appear to be blind (5). Although light-dependent release of histamine from photoreceptors has not yet been demonstrated, exposure of the fly postsynaptic neuron to histamine mimics the effects of light (6).…”

Section: From the Merck Research Laboratories Merck And Co Inc Rmentioning

confidence: 99%

Identification of Two Novel Drosophila melanogaster Histamine-gated Chloride Channel Subunits Expressed in the Eye

Hirschberg

Yuan

et al. 2002

Journal of Biological Chemistry

156

151

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Histamine has been shown to play a role in arthropod vision; it is the major neurotransmitter of arthropod photoreceptors. Histamine-gated chloride channels have been identified in insect optic lobes. We report the first isolation of cDNA clones encoding histamine-gated chloride channel subunits from the fruit fly Drosophila melanogaster. The encoded proteins, HisCl1 and HisCl2, share 60% amino acid identity with each other. The closest structural homologue is the human glycine ␣3 receptor, which shares 45 and 43% amino acid identity respectively. Northern hybridization analysis suggested that hisCl1 and hisCl2 mRNAs are predominantly expressed in the insect eye. Oocytes injected with in vitro transcribed RNA, encoding either HisCl1 or HisCl2, produced substantial chloride currents in response to histamine but not in response to GABA, glycine, and glutamate. The histamine sensitivity was similar to that observed in insect laminar neurons. Histamine-activated currents were not blocked by picrotoxinin, fipronil, strychnine, or the H2 antagonist cimetidine. Co-injection of both hisCl1 and hisCl2 RNAs resulted in expression of a histamine-gated chloride channel with increased sensitivity to histamine, demonstrating coassembly of the subunits. The insecticide ivermectin reversibly activated homomeric HisCl1 channels and, more potently, HisCl1 and HisCl2 heteromeric channels.Histamine has been recognized for several years as the major neurotransmitter of arthropod photoreceptors (1, 2). In Drosophila, immunocytochemistry has shown high levels of histamine in photoreceptors and their synapses (2, 3). Further, histidine decarboxylase activity has been demonstrated in Drosophila photoreceptors, suggesting that histamine is synthesized in these cells (2). Drosophila mutants that are deficient in the hdc gene coding for histamine decarboxylase have been identified (4), and flies homozygous for the null mutation appear to be blind (5). Although light-dependent release of histamine from photoreceptors has not yet been demonstrated, exposure of the fly postsynaptic neuron to histamine mimics the effects of light (6).Phototransduction of invertebrates has been most extensively studied in insects, but histamine has been implicated as a neurotransmitter in photoreceptors of several other invertebrate species including barnacles and the horseshoe crab Limulus (7,8), whereas glycine and GABA 1 function as the inhibitory neurotransmitters in vertebrate phototransduction (9). Outside of phototransduction, histamine also appears to be the neurotransmitter in some mechanosensory neurons in Drosophila (10) and in lobster stomatogastric, cardiac, and olfactory neurons (11-13). To date, the molecular nature of the histamine receptor in these neurons is unknown. The laminar neurons that are postsynaptic to insect photoreceptors respond to light with a rapid, chloride-mediated hyperpolarization that can be mimicked by application of histamine (6). These laminar neurons were isolated from optic lobes of several insect species, and the hista...

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Section: From the Merck Research Laboratories Merck And Co Inc Rmentioning

confidence: 99%

Identification of Two Novel Drosophila melanogaster Histamine-gated Chloride Channel Subunits Expressed in the Eye

Hirschberg

Yuan

et al. 2002

Journal of Biological Chemistry

156

151

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“…The ON and OFF transients of the ERG reflect synaptic transmission between photoreceptor terminals and second-order neurons in the lamina and medulla (Burg et al, 1993), and the amplitude of these events represents a crude measure of synaptic transmission. Although not statistically significant from controls, the ON and OFF transient amplitudes of the ERG were found to be mildly reduced in SNAP M4 hemizygotes relative to controls (Fig.…”

Section: Altering Snap Dosage Attenuates Synaptic Transmissionmentioning

confidence: 99%

Genetic Analysis of SolubleN-Ethylmaleimide-Sensitive Factor Attachment Protein Function inDrosophilaReveals Positive and Negative Secretory Roles

Babcock¹,

Macleod²,

Leither³

et al. 2004

J. Neurosci.

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The N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP) are cytosolic factors that promote vesicle fusion with a target membrane in both the constitutive and regulated secretory pathways. NSF and SNAP are thought to function by catalyzing the disassembly of a SNAP receptor (SNARE) complex consisting of membrane proteins of the secretory vesicle and target membrane. Although studies of NSF function have provided strong support for this model, the precise biochemical role of SNAP remains controversial. To further explore the function of SNAP, we have used mutational and transgenic approaches in Drosophila to investigate the effect of altered SNAP dosage on neurotransmitter release and SNARE complex metabolism. Our results indicate that reduced SNAP activity results in diminished neurotransmitter release and accumulation of a neural SNARE complex. Increased SNAP dosage results in defective synapse formation and a variety of tissue morphological defects without detectably altering the abundance of neural SNARE complexes. The SNAP overexpression phenotypes are enhanced by mutations in other secretory components and are at least partially overcome by co-overexpression of NSF, suggesting that these phenotypes derive from a specific perturbation of the secretory pathway. Our results indicate that SNAP promotes neurotransmitter release and SNARE complex disassembly but inhibits secretion when present at high abundance relative to NSF.

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“…Histamine is a biogenic amine synthesized from L-histidine via a single decarboxylation step by histidine decarboxylase (hdc) (Burg et al, 1993). In invertebrates, histamine has various roles in neurotransmission in the brain, such as olfaction in crustaceans and photoreception in various arthropods (Hardie, 1989;McClintock and Ache, 1989;Stuart, 1999), as well as in mechanoreception (Melzig et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Histamine and Its Receptors Modulate Temperature-Preference Behaviors inDrosophila

et al. 2006

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Temperature profoundly influences various life phenomena, and most animals have developed mechanisms to respond properly to environmental temperature fluctuations. To identify genes involved in sensing ambient temperature and in responding to its change, Ͼ27,000 independent P-element insertion mutants of Drosophila were screened. As a result, we found that defects in the genes encoding for proteins involved in histamine signaling [histidine decarboxylase (hdc), histamine-gated chloride channel subunit 1 (hisCl1), ora transientless (ort)] cause abnormal temperature preferences. The abnormal preferences shown in these mutants were restored by genetic and pharmacological rescue and could be reproduced in wild type using the histamine receptor inhibitors cimetidine and hydroxyzine. Spatial expression of these genes was observed in various brain regions including pars intercerebralis, fan-shaped body, and circadian clock neurons but not in dTRPA1-expressing neurons, an essential element for thermotaxis. We also found that the histaminergic mutants showed reduced tolerance for high temperature and enhanced tolerance for cold temperature. Together, these results suggest that histamine signaling may have important roles in modulating temperature preference and in controlling tolerance of low and high temperature.

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Genetic and molecular identification of a Drosophila histidine decarboxylase gene required in photoreceptor transmitter synthesis.

Cited by 118 publications

References 47 publications

Identification of Two Novel Drosophila melanogaster Histamine-gated Chloride Channel Subunits Expressed in the Eye

Identification of Two Novel Drosophila melanogaster Histamine-gated Chloride Channel Subunits Expressed in the Eye

Genetic Analysis of SolubleN-Ethylmaleimide-Sensitive Factor Attachment Protein Function inDrosophilaReveals Positive and Negative Secretory Roles

Histamine and Its Receptors Modulate Temperature-Preference Behaviors inDrosophila

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