TY - JOUR TI - The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons AU - Miller-Fleming, Tyne W AU - Petersen, Sarah C AU - Manning, Laura AU - Matthewman, Cristina AU - Gornet, Megan AU - Beers, Allison AU - Hori, Sayaka AU - Mitani, Shohei AU - Bianchi, Laura AU - Richmond, Janet AU - Miller, David M, III A2 - Shen, Kang VL - 5 PY - 2016 DA - 2016/07/12 SP - e14599 C1 - eLife 2016;5:e14599 DO - 10.7554/eLife.14599 UR - https://doi.org/10.7554/eLife.14599 AB - 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. KW - synaptic remodeling KW - calcium signaling KW - cation channel JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -