Regulation 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 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.
Cai
Ting
T
Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614, USA.
Wang
Haojie
H
Chen
Yiliang
Y
Liu
Lijun
L
Gunning
William T
WT
Quintas
Luis Eduardo M
LE
Xie
Zi-Jian
ZJ
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D021941:Caveolae / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D031541:Fluorescence Resonance Energy Transfer; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D051242:Caveolin 1; D020033:Protein Isoforms; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D000090802:rab7 GTP-Binding Proteins; D019061:src-Family Kinases; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase
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