Sodium leak channel non-selective protein (NALCN) was first described as a voltage-independent, cation-nonselective channel which is permeable to sodium, potassium and calcium ions [], however, it was recently reported to be selective only for monovalent cations and to be blocked by extracellular divalent cations []. Coexpression of NALCN, UNC79, UNC80, and NALF1 results in voltage-dependent NALCN currents [, ]. It is responsible for the background sodium ion leak current in neurons and controls neuronal excitability. It is activated either by neuropeptides substance P or neurotensin []. NALCN is required for normal respiratory rhythm and neonatal survival [].
This family consists of the auxiliary components of the NALCN sodium channel complex, NALCN channel auxiliary factor 1/2 (NALF1/2, previously known as FAM155A and FAM155B). NALCN sodium channel complex regulates the resting membrane potential and controls neuronal excitability [].
The NALCN cation channel, which controls neuronal excitability, can be activated by a reduction in extracellular calcium ions. Its activation in neurons requires the proteins UNC79 and UNC80, where UNC79 indirectly associates with NALCN through its interaction with UNC80 [].
This entry represents the central region of protein UNC80 from eukaryotes, a component of the NALCN sodium channel complex. NALCN is a cation voltage-independent channel activated by substance P, neurotensin, acetylcholine and noradrenaline that controls neuronal excitability. UNC80 forms a complex with UNC79 and both are key regulators of the channel and required for the proper expression and axonal localisation of NALCN. UNC80 is required for NALCN control by GPCRs and essential for its sensitivity to extracellular calcium. This protein acts as a scaffold for Src family of tyrosine kinases (SFK) and UNC-79 to mediate interaction with NALCN [, , ]. Proteins containing this domain also include some uncharacterised proteins from fungi.
UNC80 is a protein associated with the NALCN sodium channel complex, and is required for the activation of this channel by the neuropeptide substance P. NALCN activation is G-protein-independent, but requires Src kinases. NUNC80 binds Src kinases and recruits Src into the channel complex []. UNC80 is required for the proper localisation of C. elegans NCA-1 and NCA-2, the homologues of the vertebrate cation leak channel NALCN []. NCA-1 and UNC-80 regulate neuronal activity in C. elegans [].This entry represents the N-terminal domain of UNC80.
This entry represents the C-terminal domain of protein UNC80 from eukaryotes, a component of the NALCN sodium channel complex. NALC is a cation voltage-independent channel activated by substance P, neurotensin, acetylcholine and noradrenaline that controls neuronal excitability. UNC80 forms a complex with UNC79 and both are key regulators of the channel and required for the proper expression and axonal localisation of NALCN. UNC80 is required for NALCN control by GPCRs and essential for its sensitivity to extracellular calcium. This protein acts as a scaffold for Src family of tyrosine kinases (SFK) and UNC-79 to mediate interaction with NALCN [, , ].
