biostudies-literatureCai TNHLBI NIH HHSNIGMS NIH HHS1153-69https://www.ebi.ac.uk/biostudies/studies/S-EPMC2542476biostudies-literatureUnknown182(6)Here, we show that the Na/K-ATPase interacts with caveolin-1 (Cav1) and regulates Cav1 trafficking. Graded knockdown of Na/K-ATPase decreases the plasma membrane pool of Cav1, which results in a significant reduction in the number of caveolae on the cell surface. These effects are independent of the pumping function of Na/K-ATPase, and instead depend on interaction between Na/K-ATPase and Cav1 mediated by an N-terminal caveolin-binding motif within the ATPase alpha1 subunit. Moreover, knockdown of the Na/K-ATPase increases basal levels of active Src and stimulates endocytosis of Cav1 from the plasma membrane. Microtubule-dependent long-range directional trafficking in Na/K-ATPase-depleted cells results in perinuclear accumulation of Cav1-positive vesicles. Finally, Na/K-ATPase knockdown haThe Journal of cell biologyRegulation of caveolin-1 membrane trafficking by the Na/K-ATPase.PMC2542476P01 HL036573GM-78565R01 GM078565HL-36573R01 HL067963Cai TLiu LQuintas LEGunning WTChen YWang HXie ZJfalseRegulation of caveolin-1 membrane trafficking by the Na/K-ATPase.Here, we show that the Na/K-ATPase interacts with caveolin-1 (Cav1) and regulates Cav1 trafficking. Graded knockdown of Na/K-ATPase decreases the plasma membrane pool of Cav1, which results in a significant reduction in the number of caveolae on the cell surface. These effects are independent of the pumping function of Na/K-ATPase, and instead depend on interaction between Na/K-ATPase and Cav1 mediated by an N-terminal caveolin-binding motif within the ATPase alpha1 subunit. Moreover, knockdown of the Na/K-ATPase increases basal levels of active Src and stimulates endocytosis of Cav1 from the plasma membrane. Microtubule-dependent long-range directional trafficking in Na/K-ATPase-depleted cells results in perinuclear accumulation of Cav1-positive vesicles. Finally, Na/K-ATPase knockdown ha2008-01-01T00:00:00Z2008 Sep2025-04-04T13:11:14.395Z2019-03-27T00:16:41ZS-EPMC25424761879432810.1083/jcb.200712022