The Polarized Distribution of the Na+,K+-ATPase

The life of a cell depends on the perennial inflow of metabolites and outflow of catabolites, ultimately driven by membrane pumps or by the electrochemical potential gradients that these pumps generate. Metazoans have cells in which pumps have an additional function: they accumulate in a certain domain of the membrane to induce polarity. Surprisingly, the polarized distribution of Na+,K+-ATPase does not arise only from canonical signals or classical mechanisms but also from the peculiar affinities between its own subunits. For example, subunits α and β have an affinity for each other that binds them together right after synthesis, and they then migrate through the endoplasmic reticulum and the Golgi apparatus and are delivered to the plasma membrane. In keeping with this role of subunit affinities, we have shown that the polarized distribution of the whole enzyme at the plasma membrane facing the intercellular space arises from the very specific affinity of one β subunit for another. In addition to being distributed in a polarized manner, Na+,K+-ATPase participates in cell polarization by acting as a receptor for the ouabain hormone, thereby promoting ciliogenesis; obviously, the enzyme can act as a receptor because this is polarized toward the blood side where hormones come from. In this chapter, we review the polarized distribution of Na+,K+-ATPase and suggest that the very existence of higher metazoans depends on this polarized expression of pumps.