Na,K-ATPase Expression Can Be Limited Post-Transcriptionally: A Test of the Role of the Beta Subunit, and a Review of Evidence

The Na,K-ATPase is an alpha-beta heterodimer. It is well known that the Na,K-ATPase beta subunit is required for the biosynthesis and trafficking of the alpha subunit to the plasma membrane. During investigation of properties of human ATP1A3 mutations in 293 cells, we observed a reciprocal loss of endogenous ATP1A1 when expressing ATP1A3. Scattered reports going back as far as 1991 have shown that experimental expression of one subunit can result in reduction in another, suggesting that the total amount is strictly limited. It seems logical that either alpha or beta subunit should be rate-limiting for assembly and functional expression. Here, we present evidence that neither alpha nor beta may be limiting and that there is another level of control that limits the amount of Na,K-ATPase to physiological levels. We propose that alpha subunits compete for something specific, like a private chaperone, required to finalize their biosynthesis or to prevent their degradation in the endoplasmic reticulum.