REGULATION OF EXPRESSION AND FUNCTION BY SUBUNITS OF OLIGOMERIC P-TYPE ATPASES

Na,K-ATPase activity must be finely controlled to meet the constantly changing physiological demands and to avoid destabilization of body ho meostasis. Recent experimental evidence suggests that certain regulato ry mechanisms are closely linked to the multisubunit structure of the Na,K-pump molecule. Na,K-ATPase is composed of a catalytic alpha and a glycoprotein beta subunit and sometimes of a third component, the gam ma subunit. The beta subunit is a fundamental element of Na,K-ATPase i n that its assembly in the ER is required for the structural and funct ional maturation of the catalytic alpha subunit and in consequence the beta subunit controls the expression of functional pumps at the cell surface. Furthermore, beta subunits influence the transport properties of the mature catalytic a subunits. Distinct interaction sites mediat e the two functions of the beta subunit. Recently, we have started to characterize the gamma subunit, the functional role of which is yet no t known. Immuno-radiolabeling of epitope-tagged gamma subunits express ed in Xenopus oocytes shows that the gamma subunit is a type I membran e protein which specifically associates only with Na,K-ATPase but not with other oligomeric P-type ATPases. The gamma peptide does not influ ence the formation or the cell surface expression of functional alpha- beta complexes. On the other hand, the gamma peptide itself needs asso ciation with Na,K-ATPase to be stably expressed and to be efficiently transported to the plasma membrane. Finally, the gamma subunit can mod ulate the K activation of Na,K-pumps. Ln conclusion, processes such as subunit assembly or the subunit composition of the cell surface expre ssed Na,K-pumps appear to cooperate with hormones in the control of th e expression and the activity of Na,K-ATPase.