title: NLF-1 delivers a sodium leak channel to regulate neuronal excitability and modulate rhythmic locomotion.
abstract: A cation channel NCA/UNC-79/UNC-80 affects neuronal activity. We report here the identification of a conserved endoplasmic reticulum protein NLF-1 (NCA localization factor-1) that regulates neuronal excitability and locomotion through the NCA channel. In C. elegans, the loss of either NLF-1 or NCA leads to a reduced sodium leak current, and a hyperpolarized resting membrane potential in premotor interneurons. This results in a decreased premotor interneuron activity that reduces the initiation and sustainability of rhythmic locomotion. NLF-1 promotes axonal localization of all NCA reporters. Its mouse homolog mNLF-1 functionally substitutes for NLF-1 in C. elegans, interacts with the mammalian sodium leak channel NALCN in vitro, and potentiates sodium leak currents in primary cortical neuron cultures. Taken together, an ER protein NLF-1 delivers a sodium leak channel to maintain neuronal excitability and potentiates a premotor interneuron network critical for C. elegans rhythmic locomotion.
authors.affiliation: Institute of Medical Science, University of Toronto, ON M5S 1A8, Canada.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Shangbang
authors.initials: S
authors.lastname: Gao
authors.forename: Salvador M
authors.initials: SM
authors.lastname: Alcaire
authors.forename: Kyota
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Griffin
authors.forename: Igor
authors.initials: I
authors.lastname: Stagljar
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagamatsu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055785:Gene Knockdown Techniques / Q000379:methods; D007473:Ion Channels; D008124:Locomotion / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins; D010507:Periodicity; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C494527:C2CD4A protein, human; D029742:Caenorhabditis elegans Proteins; D007473:Ion Channels; D008565:Membrane Proteins; C544681:NALCN protein, human; D009687:Nuclear Proteins; D015222:Sodium Channels; D014157:Transcription Factors