The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons

Tyne W. Miller-Fleming, Sarah C. Petersen, Laura Manning, Cristina Matthewman, Megan Gornet, Allison Beers, Sayaka Hori, Shohei Mitani, Laura Bianchi, Janet Richmond, David M. Miller

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Article numbere14599
JournaleLife
Volume5
Issue numberJULY
DOIs
StatePublished - Jul 12 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Miller-Fleming, T. W., Petersen, S. C., Manning, L., Matthewman, C., Gornet, M., Beers, A., Hori, S., Mitani, S., Bianchi, L., Richmond, J., & Miller, D. M. (2016). The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons. eLife, 5(JULY), [e14599]. https://doi.org/10.7554/eLife.14599