title: Regulation of alpha1 Na/K-ATPase expression by cholesterol.
abstract: We have reported that α1 Na/K-ATPase regulates the trafficking of caveolin-1 and consequently alters cholesterol distribution in the plasma membrane. Here, we report the reciprocal regulation of α1 Na/K-ATPase by cholesterol. Acute exposure of LLC-PK1 cells to methyl β-cyclodextrin led to parallel decreases in cellular cholesterol and the expression of α1 Na/K-ATPase. Cholesterol repletion fully reversed the effect of methyl β-cyclodextrin. Moreover, inhibition of intracellular cholesterol trafficking to the plasma membrane by compound U18666A had the same effect on α1 Na/K-ATPase. Similarly, the expression of α1, but not α2 and α3, Na/K-ATPase was significantly reduced in the target organs of Niemann-Pick type C mice where the intracellular cholesterol trafficking is blocked. Mechanistically, decreases in the plasma membrane cholesterol activated Src kinase and stimulated the endocytosis and degradation of α1 Na/K-ATPase through Src- and ubiquitination-dependent pathways. Thus, the new findings, taken together with what we have already reported, revealed a previously unrecognized feed-forward mechanism by which cells can utilize the Src-dependent interplay among Na/K-ATPase, caveolin-1, and cholesterol to effectively alter the structure and function of the plasma membrane.
authors.affiliation: Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, Ohio 43614-2598, USA.
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Ye
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.forename: Runming
authors.initials: R
authors.lastname: Jing
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000818:Animals; D001692:Biological Transport; D051242:Caveolin 1; D002462:Cell Membrane / Q000737:chemistry; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D004705:Endocytosis; D018374:LLC-PK1 Cells; D051379:Mice; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine; D054875:Ubiquitination; D047392:beta-Cyclodextrins / Q000494:pharmacology; D019061:src-Family Kinases
chemical_list: D051242:Caveolin 1; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D019061:src-Family Kinases; D000254:Sodium-Potassium-Exchanging ATPase