Postsynaptic PKA controls quantal size and reveals a retrograde signal that regulates presynaptic transmitter release in Drosophila.
Two distinct mechanisms regulate synaptic efficacy at the Drosophila neuromuscular junction (NMJ): a PKA-dependent modulation of quantal size and a retrograde regulation of presynaptic release. Postsynaptic expression of a constitutively active PKA catalytic subunit decreases quantal size, whereas overexpression of a mutant PKA regulatory subunit (inhibiting PKA activity) increases quantal size. Increased PKA activity also decreases the response to direct iontophoresis of glutamate onto postsynaptic receptors. The PKA-dependent modulation of quantal size requires the presence of the muscle-specific glutamate receptor DGluRIIA, since PKA-dependent modulation of quantal size is lost in homozygous viable DGluRIIA- mutants. Furthermore, elevated postsynaptic PKA reduces the quantal amplitude and the time constant of miniature excitatory junctional potential (mEJP) decay to values that are nearly identical to those observed in DGluRIIA mutants. The PKA-dependent reduction in quantal size is accompanied developmentally by an increase in presynaptic quantal content, indicating the presence of a retrograde signal that regulates presynaptic release.
Davis
G W
GW
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
DiAntonio
A
A
Petersen
S A
SA
Goodman
C S
CS
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D009046:Motor Neurons / Q000201:enzymology; D016296:Mutagenesis; D009469:Neuromuscular Junction / Q000201:enzymology; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000201:enzymology*; D017470:Receptors, Glutamate / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology
D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D017868:Cyclic AMP-Dependent Protein Kinases