The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons
- Vanderbilt University, United States
- Kenyon College, United States
- University of Illinois at Chicago, United States
- University of Miami, United States
- Tokyo Women's Medical University, Japan
Abstract
Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons.
Article and author information
Author details
David M Miller III
Reviewing Editor
- Kang Shen, Howard Hughes Medical Institute, Stanford University, United States
Version history
- Received: January 21, 2016
- Accepted: July 11, 2016
- Accepted Manuscript published: July 12, 2016 (version 1)
- Version of Record published: August 10, 2016 (version 2)
- Version of Record updated: August 4, 2017 (version 3)
Copyright
© 2016, Miller-Fleming et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons
eLife 5:e14599.
https://doi.org/10.7554/eLife.14599
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