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Two cDNAs coding for histamine-gated ion channels in D. melanogaster

Nature Neuroscience volume 5, pages 1112 (2002) | Download Citation



Histamine, a neurotransmitter and neuroregulatory compound in diverse species1, serves as the neurotransmitter of photoreceptors in insects and other arthropods by directly activating a chloride channel2. By systematic expression screening of novel putative ligand-gated anion channels predicted from the Drosophila genome project, we identified two cDNAs (DM-HisCl-α1 and -α2) coding for putative histamine-gated chloride channels by functional expression in Xenopus laevis oocytes. DM-HisCl-α1 mRNA localizes in the lamina region of the Drosophila eye, supporting the idea that DM-HisCl-α1 may be a neurotransmitter receptor for histamine in the visual system.

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We thank S. Wagner, A. Stoeck, T. Sobik, M. Bathen and R. Kolarow for technical assistance, and B. Ache and K.F. Störtkuhl for comments on the manuscript.

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  1. Lehrstuhl für Zellphysiologie, Ruhr-Universität Bochum, Universitätsstraße 150, D-44780 Bochum, Germany

    • Günter Gisselmann
    • , Hermann Pusch
    •  & Hanns Hatt
  2. AG Molekulare Zellbiochemie, Ruhr-Universität Bochum, Universitätsstraße 150, D-44780 Bochum, Germany

    • Bernd T. Hovemann


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Corresponding author

Correspondence to Günter Gisselmann.

Supplementary information

Image files

  1. 1.

    Supplementary Figure 1.Amino acid alignment.

    (a)Tree structure of putative ligand-gated ion channel proteins predicted by the data of the genome sequencing project (all accession numbers beginning with AAF) and already known channel proteins (Rdl: M69057, LCCH3: S62717, Grd: X78349, GluCl: AF297500). The tree was constructed by the program megalign of the Lasergene program package.

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  1. 1.


    Amino-acid alignment with DM-HisCl-α1 (AF435469), DM-HisCl-α2 (AF435470), GABA receptor Rdl (M69057), glutamate receptor GluCl (AF297500), the C. elegans serotonin receptor MOD-1 (AF303088) and the murine glycine receptor α1 subunit (C49970). The putative DM-HisCl-α1 protein contains hydrophobic N-terminal residues with sequences highly predictive of a signal cleavage site (http:\\ which would result in a mature protein beginning at amino-acid residue 22.The putative signal cleavage site in the DM-HisCl-α2 polypeptide is located at pos. 23 and 24. The DM-HisCl-α proteins contain consensus sites for protein kinase C and casein kinase II located between M3 and M4 as well as N-linked glycosylation sites in the proposed extracellular domain (http:\\ The conserved motifs characteristic of the 'cys-brigde' family of channels, such as a large N-terminal extracellular domain and four hydrophobic transmembrane domains M1-M4, also occur in DM-HisCl-α. The main difference between DM-HisCl-α1 and DM-HisCl-α2 is the large intracellular loop between M3 and M4, which is considerably shorter in DM-HisCl-α2. The protein alignment shows that the DM-HisCl-α proteins are related to Drosophila glutamate- and GABA-gated chloride channels. Similarity to the Drosophila GABA- or glutamate-gated chloride channels Rdl {4942} and GluCl {1677} ranges from 19 to 27% of identical amino acids. Labels above the lines: putative signal sequence, M1-M4 regions, Cys-Cys bridge; ♦ N-glycosylation, ▪ PKC.

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    Alignment of the M2 regions of DM-HisCl-α1/-α2 with the ligand-gated chloride channels Rdl, GluCl, MOD-1 and Gly-alpha1 and the serotonin- and acetylcholine-gated cation channels GP-5HT3As (AF006462) and rat-nAChRαM (X03986). The putative pore-forming M2 regions of HisCl-α are more similar to the M2 regions of other ligand-gated chloride channels from Drosophlia, such as Rdl and GluCl, than to those of ligand-gated cation channels, suggesting that the DM-HisCl-α pore may also be chloride-selective.

  3. 3.

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