A neurotransmitter transporter encoded by the Drosophila  inebriated gene

Abstract

Behavioral and electrophysiological studies on mutants defective in the Drosophila inebriated (ine) gene demonstrated increased excitability of the motor neuron. In this paper, we describe the cloning and sequence analysis of ine. Mutations in ine were localized on cloned DNA by restriction mapping and restriction fragment length polymorphism (RFLP) mapping of ine mutants. DNA from the ine region was then used to isolate an ine cDNA. In situ hybridization of ine transcripts to developing embryos revealed expression of this gene in several cell types, including the posterior hindgut, Malpighian tubules, anal plate, garland cells, and a subset of cells in the central nervous system. The ine cDNA contains an open reading frame of 658 amino acids with a high degree of sequence similarity to members of the Na ؉ ͞Cl ؊ -dependent neurotransmitter transporter family. Members of this family catalyze the rapid reuptake of neurotransmitters released into the synapse and thereby play key roles in controlling neuronal function. We conclude that ine mutations cause increased excitability of the Drosophila motor neuron by causing the defective reuptake of the substrate neurotransmitter of the ine transporter and thus overstimulation of the motor neuron by this neurotransmitter. From this observation comes a unique opportunity to perform a genetic dissection of the regulation of excitability of the Drosophila motor neuron.

Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways

“…amn encodes a putative neuropeptide related to the pituitary adenylate cyclase activator peptide (PACAP; ref. 10), whereas ine encodes a putative Na ϩ ͞Cl Ϫ -dependent neurotransmitter transporter and is likely to be required for reuptake of a substrate neurotransmitter (11)(12)(13). These observations suggest that perineurial glial growth is controlled by two distinct neurotransmitters.…”

“…The genetic interactions that form the basis for this interpretation require that the mutations under investigation be null. Although the eag 1 mutation tested has not been characterized molecularly, the mutations in each of the other four genes that we analyzed are known to be or are strongly suspected to be null (11,15,25, this study). Direct neuron-perineurial glia signaling is unlikely because the peripheral glia, which form the blood-brain barrier, are expected to be an impervious barrier to intercellular traffic.…”

“…Mutations in two genes that affect neuronal excitability also affect the structure of the peripheral nerve: double mutants defective in inebriated (ine), which encodes a member of the Na ϩ ͞Cl Ϫ -dependent neurotransmitter transporter family (11)(12)(13), and pushover (push) exhibit an extremely thickened nerve, which is a phenotype that is clearly visible with the dissecting microscope. To understand the cellular basis for this phenotype, we per- Locations of the axon, peripheral glial, and perineurial glial layers are indicated.…”

Impacts of a newly identified behaviour-altering trematode on its host amphipod: from the level of gene expression to population

“…Ine2 is a neurotransmitter in Drosophila that resembles Na + /Cl − -dependent neurotransmitters, a family of transporters responsible for catalysing the rapid reuptake and release of neurotransmitters, such as serotonin, dopamine and norepinephrine, into the synapse (Soehnge et al 1996). These neurotransmitters appear to play important roles in regulating behaviour.…”

Phosphatidylinositol 3-Kinase and Akt Nonautonomously Promote Perineurial Glial Growth inDrosophilaPeripheral Nerves

“…These genes include Nf1, which is the Drosophila ortholog of human Nf1, push, which is thought to encode an E3 ubiquitin ligase and two genes implicated in neurotransmitter signaling: amnesiac, which is thought to encode a neuropeptide similar to vertebrate pituitary adenylate cyclase-activating polypeptide (Feany and Quinn, 1995), and inebriated (ine), which encodes a member of the Na ϩ /Cl Ϫ -dependent neurotransmitter transporter family (Soehnge et al, 1996). Some of these genes might regulate perineurial glial growth via the activity of Ras or PI3K within peripheral glia.…”