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10:34
A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
A presynaptic ENaC channel drives homeostatic plasticity
Meg A Younger1, Martin Müller, Amy Tong
1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-0822, USA.
Neuron
|August 27, 2013
Summary
Two genes, pickpocket11 and pickpocket16, are crucial for synaptic homeostasis in Drosophila. These genes encode Degenerin/Epithelial Sodium channels that regulate neurotransmitter release via presynaptic voltage modulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Synaptic homeostasis is vital for stable neural circuit function.
- Presynaptic neurotransmitter release is tightly regulated.
- Degenerin/Epithelial Sodium channels (DEG/ENaC) are implicated in ion transport.
Purpose of the Study:
- To identify genes involved in homeostatic modulation of neurotransmitter release.
- To elucidate the molecular mechanisms underlying synaptic homeostasis at the Drosophila neuromuscular junction (NMJ).
Main Methods:
- Electrophysiology-based forward genetic screen in Drosophila.
- Gene expression analysis (cotranscription and upregulation).
- Pharmacological inhibition of DEG/ENaC channels.
- Presynaptic calcium imaging.
Main Results:
- Identified pickpocket11 (ppk11) and pickpocket16 (ppk16) as essential for synaptic homeostasis.
- ppk11 and ppk16 are cotranscribed and upregulated during homeostatic plasticity.
- Inhibition of PPK11/PPK16 channels specifically affects homeostatic plasticity, not baseline release.
- A model where PPK11/PPK16 channels modulate membrane voltage and calcium activity was supported.
Conclusions:
- PPK11 and PPK16 are key presynaptic regulators of synaptic homeostasis.
- DEG/ENaC channels containing PPK11 and PPK16 play a specific role in homeostatic plasticity.
- These channels regulate neurotransmitter release by controlling presynaptic calcium influx through membrane voltage modulation.
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