NLF-1 Delivers a Sodium Leak Channel to Regulate Neuronal Excitability and Modulate Rhythmic Locomotion

SummaryA 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.

► Conserved ER proteins NLF-1/mNLF-1 regulate RMP and neuronal excitability ► NLF-1 delivers the NCA channel that conducts sodium leak ► NLF-1/mNLF-1 potentiates premotor interneurons ► Premotor interneuron activity sustains rhythmic locomotion