The sodium-leak channel NALCN forms a subthreshold sodium conductance that controls the resting membrane potentials of neurons. The auxiliary subunits of the channel and their functions in mammals are largely unknown. In this study, we demonstrate that two large proteins UNC80 and UNC79 are subunits of the NALCN complex. UNC80 knockout mice are neonatal lethal. The C-terminus of UNC80 contains a domain that interacts with UNC79 and overcomes a soma-retention signal to achieve dendritic localization. UNC80 lacking this domain, as found in human patients, still supports whole-cell NALCN currents but lacks dendritic localization. Our results establish the subunit composition of the NALCN complex, uncover the inter-subunit interaction domains, reveal the functional significance of regulation of dendritic membrane potential by the sodium-leak channel complex, and provide evidence supporting that genetic variations found in individuals with intellectual disability are the causes for the phenotype observed in patients.

钠泄漏通道 NALCN 形成亚阈值钠电导，控制神经元的静息膜电位。该通道的辅助亚基及其在哺乳动物中的功能在很大程度上是未知的。在这项研究中，我们证明两个大蛋白 UNC80 和 UNC79 是 NALCN 复合体的亚基。UNC80 基因敲除小鼠对新生儿是致命的。UNC80 的 C 端包含一个域，该域与 UNC79 相互作用并克服体细胞保留信号以实现树突定位。如在人类患者中发现的那样，缺少该域的 UNC80 仍然支持全细胞 NALCN 电流，但缺乏树突定位。我们的结果确定了 NALCN 复合物的亚基组成，揭示了亚基间相互作用域，