A Rosetta stone for analysis of human membrane protein function

Abstract

Knowledge of the function of membrane proteins in normal and pathological human organs would be helpful in understanding a wide range of disorders, but general strategies for obtaining it are constrained by the availability of tissue for study. Procuring living samples can be difficult and postmortem tissues are often degraded or preserved by methods that alter or destroy membrane protein function. Even given the integrity of these components, studies of their function face additional hurdles. Their relatively low abundance and investment by the lipid bilayer render purification and characterization challenging. The genes that encode them are often not available to allow analysis of their function by expression in heterologous systems. In addition, one needs to be able to study the properties of tissue- and disorder-specific posttranslationally modified proteins. In this issue of PNAS, Limon, Reyes-Ruiz, and Miledi (1) use two methods to address these issues. The first involves classical mRNA expression. The second utilizes a more recently developed and powerful technique that takes advantage of membrane fusion to analyze the function of proteins without the mRNA for the genes that encode them. The authors apply these methods to study ion channels from frozen and archived human postmortem brain tissue of normal and autistic subjects. This approach should provide a Rosetta stone with which to decipher the normal functions …