Another key area of interest is the sodium leak channel NALCN. This large protein is required for survival in mammals and gain- or loss-of-function mutations can result in devastating diseases. Although its sequence resembles that of well-known voltage-gated sodium and calcium channels, NALCN itself is nonfunctional. We have recently shown that NALCN is only functional when it forms a complex with three other proteins (Chua et al, Science Advances, 2020). This breakthrough enabled the first detailed functional characterisation of NALCN and led our collaborators to obtain a structure of NALCN together with its auxiliary factor FAM155A (Kschonsak et al, Nature, 2020). We continue to study the function and pharmacology, as well as disease-causing mutations of the sodium leak channel complex.
Left: Close up view of ATP bound to a P2X receptor