Gw. Davis et al., POSTSYNAPTIC PKA CONTROLS QUANTAL SIZE AND REVEALS A RETROGRADE SIGNAL THAT REGULATES PRESYNAPTIC TRANSMITTER RELEASE IN DROSOPHILA, Neuron, 20(2), 1998, pp. 305-315
Two distinct mechanisms regulate synaptic efficacy at the Drosophila n
euromuscular junction (NMJ): a PKA-dependent modulation of quantal siz
e and a retrograde regulation of presynaptic release. Postsynaptic exp
ression of a constitutively active PKA catalytic subunit decreases qua
ntal size, whereas overexpression of a mutant PKA regulatory subunit (
inhibiting PKA activity) increases quantal size. Increased PKA activit
y also decreases the response to direct iontophoresis of glutamate ont
o postsynaptic receptors. The PKA-dependent modulation of quantal size
requires the presence of the muscle-specific glutamate receptor DGluR
IIA, since PKA-dependent modulation of quantal size is lost in homozyg
ous viable DGluRIIA(-) mutants. Furthermore, elevated postsynaptic PKA
reduces the quantal amplitude and the time constant of miniature exci
tatory junctional potential (mEJP) decay to values that are nearly ide
ntical to those observed in DGluRIIA(-) mutants. The PKA-dependent red
uction in quantal size is accompanied developmentally by an increase i
n presynaptic quantal content, indicating the presence of a retrograde
signal that regulates presynaptic release.