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Review
. 2014 Jul:73:71-88.
doi: 10.1016/j.neuint.2014.03.015. Epub 2014 Apr 3.

Drosophila melanogaster as a genetic model system to study neurotransmitter transporters

Ciara A Martin  1 , David E Krantz  2
Affiliations
Review

Drosophila melanogaster as a genetic model system to study neurotransmitter transporters

Ciara A Martin et al. Neurochem Int. 2014 Jul.

Abstract

The model genetic organism Drosophila melanogaster, commonly known as the fruit fly, uses many of the same neurotransmitters as mammals and very similar mechanisms of neurotransmitter storage, release and recycling. This system offers a variety of powerful molecular-genetic methods for the study of transporters, many of which would be difficult in mammalian models. We review here progress made using Drosophila to understand the function and regulation of neurotransmitter transporters and discuss future directions for its use.

Keywords: Acetylcholine; ChT1; DAT; Dopamine; Drosophila; EAAT; GABA; GAT; Glutamate; Inebriated; Neurotransmitter transporter; Octopamine; Portabella; SERT; SLC1; SLC17; SLC18; SLC6; Serotonin; VAChT; VGAT; VGLUT; VMAT; VNUT; Vesicular transporter.

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Figures

Figure 1
Figure 1. Vesicular and plasma membrane neurotransmitter transporters
Vesicular and plasma membrane neurotransmitter transporters differ in several respects, including their localization and bioenergetics. In general, vesicular transporters localize to secretory vesicles, including synaptic vesicles in the presynaptic neurons that synthesize and release neurotransmitter. Depending on their subtype (see text) plasma membrane transporters may localize to either presynaptic neurons or surrounding glia. The movement of neurotransmitter via vesicular and plasma membrane transporters are coupled to proton and sodium gradients respectively. Vesicular transporters move protons (H) and neurotransmitter (NT) in opposite directions (antiport), using the high concentration of lumenal protons to drive transport. At the plasma membrane, sodium (Na) and neurotransmitters move in the same direction (symport).
Figure 2
Figure 2. The morphology and organization of mammalian and insect neurons
A canonical mammalian (A) and insect neuron (B) are indicated, highlighting differences in the location of dendrites: on the cell body of mammalian neurons versus a single process emanating from the soma of insect neurons that also gives rise to the axon. This morphology allows the characteristic organization of insect neurons into glomeruli (C), or larger but similarly organized ganglia, which include a cortical rind and neuropil as indicated.
Figure 3
Figure 3. The neuroanatomy of the adult fly brain
Cartoons show (A) horizontal, (B) frontal and (C) sagittal views of the fly and corresponding diagrams of the central nervous system. For simplicity, structures are labeled in one panel but color-coded to allow identification in all panels. Labeled structures include the central brain (orange), bilaterally symmetric optic lobes, the thoracic ganglion (yellow) and the cervical connective (blue), which contains both ascending and descending fibers. Ganglia within the optic lobes include the lamina (blue) and medulla (green) both of which receive projections from photoreceptors in the retina. Cells in both the lamina and medulla project to the lobula and lobula plate, indicated here as the lobular complex (pink). Major structures within the central brain include the mushroom bodies (purple), required for olfactory learning and memory and the central complex (yellow ellipsoid), which regulates some motor behaviors.
Figure 4
Figure 4. The Gal4/UAS System
The bipartite Gal4/UAS System employs separate transgenes to (A) drive expression and (B) allow specific cDNAs to be expressed, e.g. for Green Fluorescent Protein (GFP) as shown here. The Gal4 “driver” consists of a cell or tissue specific promoter e.g. for cells in the eye as shown in (A) immediately upstream of the cDNA encoding the yeast Gal4 transcription factor. Mating these lines results in a fly that contains both the Gal4 and UAS transgenes (C). In these progeny, Gal4 is expressed and binds to its UAS, which in turn drives expression of GFP in cells defined by the Gal4 promoter.
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