Assembly with the Na,K-ATPase α1 Subunit Is Required for Export of β1 and β2 Subunits from the Endoplasmic Reticulum

• Published in: Biochemistry (Easton) Vol. 48; no. 48; pp. 11421 - 11431
• Main Authors: Tokhtaeva, Elmira, Sachs, George, Vagin, Olga
• Format: Journal Article
• Language: English
• Published: American Chemical Society 08.12.2009
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi901438z

The level of the heterodimeric Na,K-ATPase is tightly controlled in epithelia to maintain appropriate transport function. The catalytic Na,K-ATPase α subunit is not able to exit the ER or catalyze ion transport unless assembled with the β subunit. However, requirements for the ER exit of the Na,K-ATPase β subunit that plays an additional, ion-transport-independent, role in intercellular adhesion are not clear. Exogenous β1 or β2 subunits expressed in renal MDCK cells replace endogenous β1 subunits in the α−β complexes in the ER, resulting in a decrease in the amount of the α1-bound endogenous β1 subunits by 47−61% with no change in the amount of α1 subunits. Disruption of the α1−β association by mutations in defined α1-interacting regions of either β1 or β2 subunits results in the ER retention and rapid degradation of unassembled mutants. Hence, the ER quality control system allows export only of assembled α−β complexes to the Golgi, thereby maintaining an equimolar ratio of α and β subunits in the plasma membrane, whereas the number of α1 subunits in the ER determines the amount of the α−β complexes.