Not alone: two examples of ion channels forming protein complexes to modulate cellular excitability

Membrane proteins such as ion channels play crucial roles in human physiology and their dysfunction is associated with a variety of diseases, such as neurological disorders and cancer. Despite recent advances in our understanding of their structure and function, many aspects of their biology remain elusive. In particular, the consequences of their association with other proteinaceous interaction partners are poorly understood. Here, I will present two projects in which we have investigated the regulation of ion channels by protein-protein interactions and their possible implications in neurodevelopmental and cancerous diseases. The first example will outline how we unraveled the molecular function, pharmacology & structure of the sodium leak channel complex, as well as the potential mechanism behind disease-causing mutations. The second example will cover our efforts to investigate why acid-sensing ion channels can display vastly different functional properties between different cell types or even within a population of e.g. glioblastoma cells.