Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

Hu, Ming; Fan, Lingzhi; Crowder, Ladonna A.; Karim, Zoubida; Murer, Heini; Moe, Orson W.

doi:10.1074/jbc.m011338200

Cited by 138 publications

(173 citation statements)

References 98 publications

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“…It was recently shown that endocytosis of NHE3 occurs primarily via clathrin-coated pits (36,37) and that clathrin-mediated endocytosis requires an intact actin cytoskeleton (38). In support of trafficking, we demonstrated that the decrease of NHE3 activity induced by CPA is inhibited by cytochalasin B, which induces cytoskeletal disorganization (31) and reportedly has per se an inhibitory effect on NHE3 (31) (for effect of cytochalasin B, see also the Results section).…”

Section: Discussionmentioning

confidence: 72%

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Sole¹,

Cerull²,

Petzke³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Regulation of renal apical Na ϩ /H ϩ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na ϩ homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N 6 -cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations Ͼ10 Ϫ8 M inactivate NHE3, whereas concentrations Ͻ10 Ϫ8 M stimulate NHE3 activity. Acute CPA-induced control of NHE3 was blocked by antagonists of A 1 adenosine receptors and inhibition of phospholipase C, pretreatment with BAPTA-AM (chelator of cellular calcium), and exposure to pertussis toxin. Stimulatory and to some extent also inhibitory CPA concentrations attenuated 8-bromo-cAMP and dopaminemediated inhibition of NHE3. BAPTA eliminated the ability of a stimulatory dose of CPA to attenuate 8-bromo-cAMP-induced suppression of NHE3 activity. Upon inhibition of protein kinase C, CPA at an inhibitory dose provoked activation of NHE3, which is partially reverted by 8-bromo-cAMP and suppressed by pre-incubation with BAPTA-AM. Cytochalasin B, an actin-modifying agent, selectively prevented downregulation but did not affect upregulation of NHE3 activity by CPA. In conclusion, these observations demonstrate that (1) CPA modulates NHE3 activity by elevation of cellular Ca 2ϩ exerting a negative control on adenylate cyclase activity, (2) protein kinase C is the determining factor leading to CPAinduced downregulation of NHE3 activity, and (3) alterations of surface NHE3 abundance may contribute to A 1 adenosine receptor-dependent inhibition of NHE3 activity.

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Section: Discussionmentioning

confidence: 72%

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Sole¹,

Cerull²,

Petzke³

et al. 2003

Journal of the American Society of Nephrology

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“…Protein kinase A-mediated phosphorylation of NHE3 was also implicated in the internalization of NHE3 after the chronic exposure of cells to hormones that elevate cAMP (3), which suggested that, in the absence of NHERF-1, NHE3 localization may be modified. However, no difference was discernable in the apical localization of NHE3 in proximal tubules from WT and NHERF-1(Ϫ͞Ϫ) mice, which could ref lect a low rate of NHE3 recycling under basal or resting conditions (41) or functional compensation by NHERF-2 to maintain NHE3 at the apical membrane. Recent studies have also suggested a direct link between NHE3 and the actin cytoskeleton (41), which may also play a role in the membrane localization and activity of the antiporter.…”

Section: Discussionmentioning

confidence: 97%

Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting

Shenolikar

Voltz

Minkoff

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

308

260

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Na ؉ ͞H ؉ exchanger regulatory factor (NHERF)-1 and NHERF-2, two structurally related protein adapters containing tandem PSD-95͞ Discs large͞ZO-1 (PDZ) domains, were identified as essential factors for protein kinase A-mediated inhibition of the sodium-hydrogen exchanger, NHE3. NHERF-1 and NHERF-2 also bound other cellular targets including the sodium-phosphate cotransporter type IIa encoded by the NPT2 gene. Targeted disruption of the mouse NHERF-1 gene eliminated NHERF-1 expression in kidney and other tissues of the mutant mice without altering NHERF-2 levels in these tissues. NHERF-1 (؉͞؊) and (؊͞؊) male mice maintained normal blood electrolytes but showed increased urinary excretion of phosphate when compared with wild-type (؉͞؉) animals. Although the overall levels of renal NHERF-1 targets, NHE3 and Npt2, were unchanged in the mutant mice, immunocytochemistry showed that the Npt2 protein was aberrantly localized at internal sites in the renal proximal tubule cells. The mislocalization of Npt2 paralleled a reduction in the transporter protein in renal brushborder membranes isolated from the mutant mice. In contrast, NHE3 was appropriately localized at the apical surface of proximal tubules in both wild-type and mutant mice. These data suggested that NHERF-1 played a unique role in the apical targeting and͞or trafficking of Npt2 in the mammalian kidney, a function not shared by NHERF-2 or other renal PDZ proteins. Phosphate wasting seen in the NHERF-1(؊͞؊) null mice provided a new experimental system for defining the role of PDZ adapters in the hormonal control of ion transport and renal disease.

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“…It is uncertain whether this ion transport is due to an increase in the intrinsic activity of the transporters and/or an increase in their number at the membrane. Indeed, NHE3 undergoes continuous recycling between the plasma membrane and the large pool of subcellular endosomes (9,10), and redistribution between these pools was suggested to contribute to the regulation of exchange activity (11). Whether the transporter trafficking is downstream of the flow stimulation, however, remains unknown.…”

mentioning

confidence: 99%

Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells

Duan

Weinstein

Weinbaum

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Our previous studies of microperfused single proximal tubule showed that flow-dependent Na + and HCO 3 − reabsorption is due to a modulation of both NHE3 and vacuolar H + -ATPase (V-ATPase) activity. An intact actin cytoskeleton was indicated to provide a structural framework for proximal tubule cells to transmit mechanical forces and subsequently modulate cellular functions. In this study, we have used mouse proximal tubule (MPT) cells as a model to study the role of fluid shear stress (FSS) on apical NHE3 and V-ATPase and basolateral Na/K-ATPase trafficking and expression. Our hypothesis is that FSS stimulates both apical and basolateral transporter expression and trafficking, which subsequently mediates salt and volume reabsorption. We exposed MPT cells to 0.2 dynes/cm 2 FSS for 3 h and performed confocal microscopy and Western blot analysis to compare the localization and expression of both apical and basolateral transporters in control cells and cells subjected to FSS. Our findings show that FSS leads to an increment in the amount of protein expression, and a translocation of apical NHE3 and V-ATPase from the intracellular compartment to the apical plasma membrane and Na/K-ATPase to the basolateral membrane. Disrupting actin by cytochalasin D blocks the FSS-induced changes in NHE3 and Na/K-ATPase, but not V-ATPase. In contrast, FSS-induced V-ATPase redistribution and expression are largely inhibited by colchicine, an agent that blocks microtubule polymerization. Our findings suggest that the actin cytoskeleton plays an important role in FSS-induced NHE3 and Na/K-ATPase trafficking, and an intact microtubule network is critical in FSS-induced modulation of V-ATPase in proximal tubule cells. , Cl − , and water reabsorption, as well as distal Na + absorption and K + secretion (1-5). In the kidney proximal tubule, glomerular tubular balance (GTB) allows for a rapid response to the changes of glomerular filtration rate (GFR) and provides for a nearly proportional change in Na + and HCO 3 − in the fluid filtered from the glomeruli (1). The physiological importance of this regulation is to prevent loss of solute following increases in GFR, and to preserve adequate distal delivery of sodium and fluid when GFR is reduced. This highly regulated uptake of Na + and HCO 3 − depends on the activity of a group of transport proteins that are located on the luminal and peritubular membrane of proximal tubule cells. Sodium reabsorption across the proximal tubule is driven by basolateral sodium pumps (Na/K-ATPase) and enters through apical NHE3. HCO 3 − reabsorption is regulated by apical transporters NHE3 and vacuolar H + -ATPase (V-ATPase) in tandem with the basolateral Na + /HCO 3 − cotransporter (NBC). We have previously investigated the role of FSS in modulating Na + and HCO 3 − reabsorption in mouse proximal tubule (MPT) using an in vitro microperfusion technique. Our findings indicated that both NHE3 (3, 6) and V-ATPase (3) activities were enhanced by increases in luminal flow rate. These experiments confirmed that bo...

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Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

Cited by 138 publications

References 98 publications

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting

Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells

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