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

摘要

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.