2022
DOI: 10.1038/s41467-022-35417-9
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A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling

Abstract: Presynaptic homeostatic plasticity (PHP) adaptively enhances neurotransmitter release following diminished postsynaptic glutamate receptor (GluR) functionality to maintain synaptic strength. While much is known about PHP expression mechanisms, postsynaptic induction remains enigmatic. For over 20 years, diminished postsynaptic Ca2+ influx was hypothesized to reduce CaMKII activity and enable retrograde PHP signaling at the Drosophila neuromuscular junction. Here, we have interrogated inductive signaling and fi… Show more

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Cited by 6 publications
(6 citation statements)
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“…In heterologous systems and in vivo , this Q to R transition renders both AMPA- and Kainate-GluRs impermeable to Ca 2+ . 13 , 30 33 GluRIIA Q615R mutants are homozygous viable and healthy, exhibit normal synaptic transmission (miniature and evoked release), and express GluRA and GluRB receptors that do not significantly change in abundance compared to wild type, 34 as expected. Thus, GluRIIA Q615R mutants render GluRA receptors Ca 2+ impermeable without impacting basal synaptic transmission or relative GluR composition or abundance.…”
Section: Resultsmentioning
confidence: 52%
See 1 more Smart Citation
“…In heterologous systems and in vivo , this Q to R transition renders both AMPA- and Kainate-GluRs impermeable to Ca 2+ . 13 , 30 33 GluRIIA Q615R mutants are homozygous viable and healthy, exhibit normal synaptic transmission (miniature and evoked release), and express GluRA and GluRB receptors that do not significantly change in abundance compared to wild type, 34 as expected. Thus, GluRIIA Q615R mutants render GluRA receptors Ca 2+ impermeable without impacting basal synaptic transmission or relative GluR composition or abundance.…”
Section: Resultsmentioning
confidence: 52%
“…Imaging was performed in modified HL-3 saline with 1.5 mM Ca 2+ added using a Nikon A1R Resonant Scanning Confocal microscope equipped with NIS Elements software and a 60x APO 1.0NA water immersion objective as detailed. 34 NMJs on muscle 6/7 were imaged at a resonant frequency of 60 fps (256 × 256 pixels). Spontaneous Ca 2+ events were recorded at 4–8 individual NMJs during 120 s imaging sessions from at least three different larvae.…”
Section: Methodsmentioning
confidence: 99%
“…To try to gain a more mechanistic understanding of how postsynaptic sra overexpression may be blocking the maintenance of PHP, we measured phosphorylated CaMKII (pCaMKII) levels and glutamate receptor signal intensity. Genetic glutamate receptor challenges normally result in decreased levels of pCaMKII immunofluorescence (Goel et al, 2017 ; Newman et al, 2017 ; Li et al, 2018 ; Kikuma et al, 2019 ; Perry et al, 2022 ), and this decrease correlates with the successful expression of PHP.…”
Section: Resultsmentioning
confidence: 99%
“…Mechanistical differences between chronic and acute forms of PHP have been increasingly discovered [49][50][51]. For the induction of chronic homeostasis, the physical loss of the C-terminal tail of GluRIIA plays a fundamental role [52]. However, the precise mechanism of acute PHP induction remains elusive.…”
Section: Discussionmentioning
confidence: 99%