Abstract
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 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport / physiology*
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Caveolae / metabolism
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Caveolae / ultrastructure
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Caveolin 1 / genetics
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Caveolin 1 / metabolism*
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Cell Membrane / metabolism*
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Cell Membrane / ultrastructure
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Cytoplasmic Vesicles / metabolism
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Endocytosis / physiology
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Fluorescence Resonance Energy Transfer
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Golgi Apparatus / metabolism
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Golgi Apparatus / ultrastructure
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Microtubules / metabolism
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Point Mutation
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Subunits / genetics
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Protein Subunits / metabolism
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RNA Interference
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Rats
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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Sodium-Potassium-Exchanging ATPase / genetics
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Sodium-Potassium-Exchanging ATPase / metabolism*
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rab GTP-Binding Proteins / genetics
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rab GTP-Binding Proteins / metabolism
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rab5 GTP-Binding Proteins / genetics
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rab5 GTP-Binding Proteins / metabolism
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rab7 GTP-Binding Proteins
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / genetics
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src-Family Kinases / metabolism
Substances
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Caveolin 1
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Protein Isoforms
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Protein Subunits
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Recombinant Fusion Proteins
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rab7 GTP-Binding Proteins
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src-Family Kinases
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rab GTP-Binding Proteins
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rab5 GTP-Binding Proteins
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Sodium-Potassium-Exchanging ATPase