title: The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons.
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.
authors.affiliation: Neuroscience Program, Vanderbilt University, Nashville, United States.
authors.forename: Tyne W
authors.initials: TW
authors.lastname: Miller-Fleming
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Petersen
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States.
authors.forename: Laura
authors.identifier: 0000-0003-1597-0600
authors.initials: L
authors.lastname: Manning
authors.affiliation: Department of Physiology and Biophysics, University of Miami, Miami, United States.
authors.forename: Cristina
authors.initials: C
authors.lastname: Matthewman
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Gornet
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
authors.forename: Allison
authors.initials: A
authors.lastname: Beers
authors.affiliation: Department of Physiology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hori
authors.affiliation: Department of Physiology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.affiliation: Department of Physiology and Biophysics, University of Miami, Miami, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States.
authors.forename: Janet
authors.initials: J
authors.lastname: Richmond
authors.affiliation: Neuroscience Program, Vanderbilt University, Nashville, United States.|Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
authors.forename: David M
authors.identifier: 0000-0001-9048-873X
authors.initials: DM
authors.lastname: Miller
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D059330:GABAergic Neurons / Q000502:physiology*; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000378:metabolism*; D009473:Neuronal Plasticity
chemical_list: D029742:Caenorhabditis elegans Proteins; D007473:Ion Channels; C104078:unc-8 protein, C elegans
keywords: C. elegans; calcium signaling; cation channel; neuroscience; synaptic remodeling