Co-localization and interaction of organic anion transporter 1 with caveolin-2 in rat kidney

Kwak, Jin-Oh; Kim, Hyun Woo; Oh, Kwang-Jin; Kim, Dong Su; Han, Kyoung-Sik; Ho, Seok

doi:10.1038/emm.2005.28

Cited by 40 publications

(37 citation statements)

References 21 publications

(27 reference statements)

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“…The evidence for this is extensive, but dynamin also regulates membrane turnover through caveolae in mammalian cells (24,25). Xenopus expresses caveolin genes (26), and there is evidence that caveolae may operate in Xenopus oocytes (27,28). Therefore, it is possible that caveolae have a role in the accelerated endocytosis of ROMK that we observed in the presence of WNK1.…”

Section: Discussionmentioning

confidence: 75%

WNK1 Affects Surface Expression of the ROMK Potassium Channel Independent of WNK4

Cope

Murthy

Golbang

et al. 2006

Journal of the American Society of Nephrology

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The WNK (with no lysine kinase) kinases are a novel class of serine/threonine kinases that lack a characteristic lysine residue for ATP docking. Both WNK1 and WNK4 are expressed in the mammalian kidney, and mutations in either can cause the rare familial syndrome of hypertension and hyperkalemia (Gordon syndrome, or pseudohypoaldosteronism type 2). The molecular basis for the action of WNK4 is through alteration in the membrane expression of the NaCl co-transporter (NCCT) and the renal outer-medullary K channel KCNJ1 (ROMK). The actions of WNK1 are less well defined, and evidence to date suggests that it can affect NCCT expression but only in the presence of WNK4. The results of co-expressing WNK1 with ROMK in Xenopus oocytes are reported for the first time. These studies show that WNK1 is able to suppress total current directly through ROMK by causing a marked reduction in its surface expression. The effect is mimicked by a kinase-dead mutant of WNK1 (368D>A), suggesting that it is not dependent on its catalytic activity. Study of the time course of ROMK expression further suggests that WNK1 accelerates trafficking of ROMK from the membrane, and this effect seems to be dynamin dependent. Using fragments of full-length WNK1, it also is shown that the effect depends on residues in the middle section of the protein (502 to 1100 WNK1) that contains the acidic motif. Together, these findings emphasize that the molecular mechanisms that underpin WNK1 regulation of ROMK expression are distinct from those that affect NCCT expression.J Am Soc Nephrol 17: 1867 -1874, 2006 . doi: 10.1681 T he WNK (with no lysine kinase) kinases WNK1 and WNK4 are widely expressed in mammalian transporting epithelia (1,2), and expression studies in Xenopus oocytes suggest that they are able to modify the expression of several co-transporters and ion channels (3,4). The details of the interaction are best understood for WNK4, which reduces surface expression of the thiazide-sensitive NaCl co-transporter (NCCT; gene symbol SLC12A3) in Xenopus oocytes (5-8). This effect of WNK4 depends on its serine-threonine (S/T) kinase activity as well as a highly conserved downstream acidic motif (EPEEPEADQH). Mutations that cause charge-changing amino acid substitutions within this motif abolish the inhibitory effect of wild-type WNK4 and cause the phenotype of hypertension and hyperkalemia that characterizes Gordon syndrome (pseudohypoaldosteronism type 2 [PHA2]; OMIM #145260) (9). WNK1 mutations also can cause this phenotype, but published data suggest that WNK1 protein is effective only in regulating NCCT trafficking when coexpressed with WNK4 (5,10). This suggests that the WNK may form a multimeric complex with NCCT and that protein-protein interactions between WNK1 and WNK4 are key to the functionality of WNK1.It is not known whether this paradigm of WNK1-WNK4 interaction extends to the effects of WNK on other transporters or ion channels. Lifton's laboratory has shown, for example, that WNK4 also inhibits expression of the Na-K-Cl cotransporter SLC1...

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Section: Discussionmentioning

confidence: 75%

WNK1 Affects Surface Expression of the ROMK Potassium Channel Independent of WNK4

Cope

Murthy

Golbang

et al. 2006

Journal of the American Society of Nephrology

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“…The parallel plate, which was incubated on a cover glass, was observed via confocal microscopy (Zeiss LSM510 Meta, Ex = 488 nm, Em = 533 nm) in order to compare the fluorescence intensity. The confocal visualization of NBDcholesterol uptake was conducted as previously described (Dagher et al, 2003;Kwak et al, 2005).…”

Section: Measurement Of Cholesterol Delivery Into Hepg2 Cellsmentioning

confidence: 99%

A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice

Cho

Park²,

Han³

et al. 2007

Exp Mol Med

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In our previous study, two point mutants of apolipoprotein A-I, designated V156K and A158E, revealed peculiar characteristics in their lipid-free and lipid-bound states. In order to determine the putative therapeutic potential of these mutants, several in vitro and in vivo evaluations were conducted. In the lipid-free state, V156K showed more profound antioxidant activity against LDL oxidation than did the wildtype (WT) or A158E variants in an in vitro assay. In the lipid-bound state, V156K-rHDL showed an enhanced cholesterol delivery activity to HepG2 cells in a time-dependent manner, as compared to WT-rHDL, A158E-rHDL, and R173C-rHDL. We assessed the physiological activities of the mutants in circulation, using hypercholesterolemic mice (C57BL6/J). Palmitoyloleoyl phosphatidylcholine (POPC)-rHDL preparations containing each of the apoA-I variants were injected into the mice at a dosage of 30 mg of apoA-I/kg of body weight. Forty eight hours after injection, the sera of the V156K-rHDL injected group showed the most potent antioxidant abilities in the ferric acid removal assay. The V156K-rHDL-or R173C-rHDL-injected mice showed no atherosclerotic lesions and manifested striking increases in their serum apo-E levels, as compared to the mice injected with WT-rHDL or A158E-rHDL. In conclusion, V156K-rHDL exhibited the most pronounced antioxidant activity and anti-atherosclerotic activity, both in vitro and in vivo. These results support the notion that HDL-therapy may prove beneficial due to its capacity to induce accelerated cholesterol excretion, as well as its enhanced antioxidant and anti-inflammatory effects and lesion regression effect.

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“…A major component of caveolae, one such lipid raft domain, is the selfassociating protein, caveolin. Recently, rOat1 was shown to co-localize with caveolin 2 in the plasma membrane of rat renal proximal tubule cells in primary culture (Kwak et al 2005a). Furthermore, decreasing expression of either caveolin 1 or 2 leads to the reduction of rOat1 and rOat3 function (Kwak et al 2005a, c).…”

Section: Regulationmentioning

confidence: 99%

Physiology, structure, and regulation of the cloned organic anion transporters

2008

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Abstract1. The transport of negatively charged drugs, xenobiotics, and metabolites by epithelial tissues, particularly the kidney, plays critical roles in controlling their distribution, concentration, and retention in the body. Thus, organic anion transporters (OATs) impact both their therapeutic efficacy and potential toxicity.2. This review summarizes current knowledge of the properties and functional roles of the cloned OATs, the relationships between transporter structure and function, and those factors that determine the efficacy of transport. Such factors include plasma protein binding of substrates, genetic polymorphisms among the transporters, and regulation of transporter expression.3. Clearly, much progress has been made in the decade since the first OAT was cloned. However, unresolved questions remain. Several of these issues -drug-drug interactions, functional characterization of newly cloned OATs, tissue differences in expression and function, and details of the nature and consequences of transporter regulation at genomic and intracellular sites -are discussed in the concluding Perspectives section.

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Co-localization and interaction of organic anion transporter 1 with caveolin-2 in rat kidney

Abstract: A bstract

Cited by 40 publications

References 21 publications

WNK1 Affects Surface Expression of the ROMK Potassium Channel Independent of WNK4

WNK1 Affects Surface Expression of the ROMK Potassium Channel Independent of WNK4

A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice

Physiology, structure, and regulation of the cloned organic anion transporters

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