Na+/K+-ATPase Drives Most Asymmetric Transports and Modulates the Phenotype of Epithelial Cells

Usually, the history of an enzyme is the narrative of the works to isolate and purify it, measure its molecular weight, determine its crystal configuration, measure its activity, and so on, along years of research. The history of the Na+/K+-ATPase is instead a tortuous road full of pitfalls, skirmishes with physical chemistry, thermodynamics, and even philosophy. Fortunately, it has a happy ending, because it was the first known molecule to produce vectorial movement of ions, at the expense of chemical energy, cyclically modifying its selectivity. Later on, its role has evolved to act as a self-adhesion molecule at cell–cell contacts, to act as a receptor of the hormone ouabain, whose main physiological role is to modulate cell contacts, to generate a Na+ gradient that enables co- and anti-transporters to transport net amount of ions, sugars, amino acids, i.e., to act as secondary pumps. It is enough to say that one of its crucial properties, i.e., to be expressed in a polarized manner at the intercellular membrane of transporting epithelial cells involves the β-subunit of the pump, that happens to be an adhesion molecule which plays a crucial role in that polarization mechanism.