[
Neuron,
2013]
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 invitro, and potentiates sodium leak currents inprimary cortical neuron cultures. Taken together, an ER protein NLF-1 delivers a sodium leak channel to maintain neuronal excitability and potentiatesa premotor interneuron network critical for C.elegans rhythmic locomotion.