Deconvoluting receptor trafficking, regulation, and function using massively parallel assays

Abstract

As with many other proteins, ion channels are tremendously complex. In normal physiology for an ion channel to function it must fold, traffic to the surface, respond to stimuli, and conduct ions. In disease, mutations breaks an ion channel by altering one of these stages. However, traditionally, we only study several mutations at a time which limits our ability to mechanistically understand the molecular basis of disease or how a protein normally functions in biology. In the inwardly rectifying potassium channel, Kir2.1, mutations give rise to developmental and cardiac disorder through altering PIP2 dependent activation, folding, and functions.