Postsynaptic PKA Controls Quantal Size and Reveals a Retrograde Signal that Regulates Presynaptic Transmitter Release in Drosophila
نویسندگان
چکیده
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.
منابع مشابه
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. Muta...
متن کاملGlutamate receptor expression regulates quantal size and quantal content at the Drosophila neuromuscular junction.
At the Drosophila glutamatergic neuromuscular junction, the postsynaptic cell can regulate synaptic strength by both changing its sensitivity to neurotransmitter and generating a retrograde signal that regulates presynaptic transmitter release. To investigate the molecular mechanisms underlying these forms of plasticity, we have undertaken a genetic analysis of two postsynaptic glutamate recept...
متن کاملCharacterization of Postsynaptic Ca 2+ Signals at the Drosophila Larval Nmj 2 3 4
22 Postsynaptic [Ca]i has been proposed to play an important role in both synaptic plasticity and 23 synaptic homeostasis. In particular, postsynaptic Ca signals can alter synaptic efficacy by 24 influencing transmitter release, receptor sensitivity and protein synthesis. We examined the 25 postsynaptic Ca transients at the Drosophila larval NMJ by injecting the muscle fibers with 26 Ca indicat...
متن کاملPresynaptic Molecular Determinants of Quantal Size
The quantal hypothesis for the release of neurotransmitters at the chemical synapse has gained wide acceptance since it was first worked out at the motor endplate in frog skeletal muscle in the 1950's. Considering the morphological identification of synaptic vesicles (SVs) at the nerve terminals that appeared to be homogeneous in size, the hypothesis proposed that signal transduction at synapse...
متن کاملCharacterization of postsynaptic Ca signals at the Drosophila larval NMJ
Desai SA, Lnenicka GA. Characterization of postsynaptic Ca signals at the Drosophila larval NMJ. J Neurophysiol 106: 710–721, 2011. First published May 18, 2011; doi:10.1152/jn.00045.2011.— Postsynaptic intracellular Ca concentration ([Ca ]i) has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. In particular, postsynaptic Ca signals can alter synapti...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Neuron
دوره 20 شماره
صفحات -
تاریخ انتشار 1998