Regulation of caveolin-1 membrane trafficking by the Na/K-ATPase

• DOI: 10.1083/jcb.200712022
• Publication Date: 2008-09-16T01:09:22Z
• Authors: Ting Cai; Haojie Wang; Yiliang Chen; Lijun Liu; William T Gunning; Luis Eduardo M. Q...; Zi-Jian Xie
• Keywords: 0303 health sciences; Recombinant Fusion Proteins; Caveolin 1; Cell Membrane; Cytoplasmic Vesicles; Golgi Apparatus; Biological Transport; Caveolae; Microtubules; Endocytosis; Rats; Protein Subunits; 03 medical and health sciences; rab GTP-Binding Proteins; Fluorescence Resonance Energy Transfer; Animals; Point Mutation; Protein Isoforms; RNA Interference; Sodium-Potassium-Exchanging ATPase; Research Articles; Signal Transduction; rab5 GTP-Binding Proteins

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 α1 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 has no effect on processing or exit of Cav1 from the Golgi. Thus, the Na/K-ATPase regulates Cav1 endocytic trafficking and stabilizes the Cav1 plasma membrane pool.