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Published online September 15, 2008
doi:10.1083/jcb.200712022
The Journal of Cell Biology, Vol. 182, No. 6, 1153-1169
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Cai et al.
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Article

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



Ting Cai1, Haojie Wang2, Yiliang Chen1, Lijun Liu1, William T Gunning3, Luis Eduardo M. Quintas4, and Zi-Jian Xie1,2

1 Department of Physiology and Pharmacology, 2 Department of Medicine, and 3 Department of Pathology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614
4 Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-902, Rio de Janeiro, Brasil

Correspondence to Zi-Jian Xie: zi-jian.xie{at}utoledo.edu

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 {alpha}1 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.

Abbreviations used in this paper: Cav1, caveolin-1; CBM, caveolin-binding motif; FRET, fluorescence resonance energy transfer; mCBM, mutated caveolin-binding motif; MSD, mean square displacement.

© 2008 Cai et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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