RRC ID 46472
Author Xie L, Gao S, Alcaire SM, Aoyagi K, Wang Y, Griffin JK, Stagljar I, Nagamatsu S, Zhen M.
Title NLF-1 delivers a sodium leak channel to regulate neuronal excitability and modulate rhythmic locomotion.
Journal Neuron
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.
Volume 77(6)
Pages 1069-82
Published 2013-3-20
DOI 10.1016/j.neuron.2013.01.018
PII S0896-6273(13)00084-6
PMID 23522043
MeSH Animals Axons / metabolism Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caenorhabditis elegans Proteins / physiology Cells, Cultured Endoplasmic Reticulum / metabolism Gene Knockdown Techniques / methods Locomotion / physiology* Mice Mice, Inbred C57BL Molecular Sequence Data Neurons / metabolism* Periodicity* Sodium Channels / genetics Sodium Channels / metabolism* Sodium Channels / physiology Transcription Factors / genetics Transcription Factors / metabolism* Transcription Factors / physiology
IF 14.319
Times Cited 18
C.elegans tm3631