Genetic analysis of glutamate receptors in Drosophila reveals a retrograde signal regulating presynaptic transmitter release.
Postsynaptic sensitivity to glutamate was genetically manipulated at the Drosophila neuromuscular junction (NMJ) to test whether postsynaptic activity can regulate presynaptic function during development. We cloned the gene encoding a second muscle-specific glutamate receptor, DGluRIIB, which is closely related to the previously identified DGluRIIA and located adjacent to it in the genome. Mutations that eliminate DGluRIIA (but not DGluRIIB) or transgenic constructs that increase DGluRIIA expression were generated. When DGluRIIA is missing, the response of the muscle to a single vesicle of transmitter is substantially decreased. However, the response of the muscle to nerve stimulation is normal because quantal content is significantly increased. Thus, a decrease in postsynaptic receptors leads to an increase in presynaptic transmitter release, indicating that postsynaptic activity controls a retrograde signal that regulates presynaptic function.
Petersen
S A
SA
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Fetter
R D
RD
Noordermeer
J N
JN
Goodman
C S
CS
DiAntonio
A
A
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004330:Drosophila; D017344:Genes, Insect; D005804:Genes, Lethal; D007814:Larva; D008969:Molecular Sequence Data; D009132:Muscles / Q000502:physiology*; D016254:Mutagenesis, Insertional; D009469:Neuromuscular Junction / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D009435:Synaptic Transmission
D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate