Presynaptic glutamic acid decarboxylase is required for induction of the postsynaptic receptor field at a glutamatergic synapse.
We have systematically screened EMS-mutagenized Drosophila for embryonic lethal strains with defects in glutamatergic synaptic transmission. Surprisingly, this screen led to the identification of several alleles with missense mutations in highly conserved regions of Dgad1. Analysis of these gad mutants reveals that they are paralyzed owing to defects in glutamatergic transmission at the neuromuscular junction. Further electrophysiological and immunohistochemical examination reveals that these mutants have greatly reduced numbers of postsynaptic glutamate receptors in an otherwise morphologically normal synapse. By overexpressing wild-type Dgad1 in selected neurons, we show that GAD is specifically required in the presynaptic neuron to induce a postsynaptic glutamate receptor field, and that the level of postsynaptic receptors is closely dependent on presynaptic GAD function. These data demonstrate that GAD plays an unexpected role in glutamatergic synaptogenesis.
Department of Biology, University of Utah, Salt Lake City 84112, USA.
D E
DE
Featherstone
E M
EM
Rushton
M
M
Hilderbrand-Chae
A M
AM
Phillips
F R
FR
Jackson
K
K
Broadie
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D004594:Electrophysiology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D018408:Patch-Clamp Techniques; D010641:Phenotype; D017661:Receptors, Presynaptic / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000201:enzymology* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018377:Neurotransmitter Agents; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase