ミタニ シヨウヘイ   MITANI Shohei
  三谷 昌平
   所属   医学部 医学科
   職種   教授・講座主任
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons.
掲載誌名 正式名:eLife
略  称:Elife
ISSNコード:(2050-084X)2050-084X(Linking)
掲載区分国外
巻・号・頁 5,e14599頁
著者・共著者 Miller-Fleming Tyne W, Petersen Sarah C, Manning Laura, Matthewman Cristina, Gornet Megan, Beers Allison, Hori Sayaka, Mitani Shohei, Bianchi Laura, Richmond Janet, Miller David M
発行年月 2016/08
概要 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.
DOI 10.7554/eLife.14599
PMID 27403890