Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

Li, Hewang; Armando, Inés; Yu, Pingfeng; Escano, Crisanto; Mueller, Susette C.; Asico, Laureano D.; Pascua, Annabelle; Lu, Quansheng; Wang, Xiaoyan; Villar, Van Anthony M.; Jones, John E.; Wang, Zheng; Periasamy, Ammasi; Lau, Yuen-Sum; Soares‐da‐Silva, Patrício; Creswell, Karen; Guillemette, Gaétan; Sibley, David R.; Eisner, Gilbert M.; Felder, Robin A.; José, Pedro A.

doi:10.1172/jci33637

Cited by 51 publications

(74 citation statements)

References 55 publications

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“…Thus, dopamine and ANG II appear to serve counterregulatory functions in the kidney (5,15,16). In this regard, dopamine inhibits renal renin expression (38) and inhibits ANG II-mediated tubule function and AT 1 expression (9,21,28,40). The goal of the present studies was to determine the potential role of intrarenal dopamine to modulate the effects of ANG II excess on renal function and development of progressive injury.…”

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confidence: 96%

Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury

Yang

Yao

Zhou

et al. 2012

American Journal of Physiology-Renal Physiology

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It is well-recognized that excessive angiotensin II (ANG II) can mediate progressive renal injury. Previous studies by us and others have indicated that dopamine may modulate actions of ANG II in the kidney. The current studies investigated whether altering intrarenal dopamine levels affected ANG II-mediated renal fibrosis. We utilized a model of increased intrarenal dopamine, catechol-O-methyl-transferase knockout (COMT KO) mice, which have increased kidney dopamine levels due to deletion of a major intrarenal dopamine-metabolizing enzyme. In wild-type mice, chronic ANG II infusion increased renal expression of both of the major dopamine-metabolizing enzymes, COMT and monoamine oxidase. After 8 wk of ANG II infusion, there were no significant differences in blood pressure between wild-type and COMT KO mice. Compared with wild-type, COMT KO mice had decreased albuminuria and tubulointerstitial injury. In response to ANG II infusion, there was decreased expression of both glomerular and tubulointerstitial injury markers (fibronectin, connective tissue growth factor, fibroblast-specific protein-1, collagen I, podocyte vascular endothelial growth factor) in COMT KO mice. We recently reported that ANG II-mediated tubulointerstitial fibrosis is mediated by src-dependent epidermal growth factor receptor (EGFR) activation. In aromatic l-amino acid decarboxylase knockout (AADC KO) mice, a model of intrarenal dopamine deficiency due to selective proximal tubule AADC deletion, which inhibits intrarenal dopamine synthesis, ANG II infusion further increased expression of p-src and pTyr845-EGFR. In contrast, their expression was markedly attenuated in COMT KO mice. These results demonstrate a role for intrarenal dopamine to buffer the detrimental effects of ANG II upon the kidney.

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confidence: 96%

Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury

Yang

Yao

Zhou

et al. 2012

American Journal of Physiology-Renal Physiology

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“…22 The lifetime of AT 1 R ͑-EGFP, the donor͒ is shortened to 1.68 ns with D 5 R stimulation, in the presence of ubiquitin as the acceptor fluorophore, suggesting that a fraction of AT 1 Rs is polyubiquitinated and processed for proteasomal degradation. 22 Our previous FRET studies showed that some of the internalized AT 1 Rs escape degradation and recycle back to the plasma membrane, coordinately, via Rab4 and Rab11 following Ang II stimulation. 26 In this study, Ang II treatment shortens the AT 1 R-EGFP lifetime, in the presence of Rab5, Rab7, and LAMP1 labeled with Alexa 555 ͑Table 2, Figs.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21] Utilizing these techniques, we reported recently that the AT 1 R is degraded in proteasomes on stimulation of the D 5 dopamine receptor ͑D 5 R͒ in human renal proximal tubule and HEK293 cells. 22 This is in contrast to the lysosomal degradation of AT 1 R on binding with its endogenous ligand, Ang II. 17,18 However, the dynamic regulation of AT 1 R degradation following Ang II stimulation is not well understood.…”

Section: Introductionmentioning

confidence: 98%

Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

2010

J. Biomed. Opt

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Abstract. The dynamic regulation of the cellular trafficking of human angiotensin ͑Ang͒ type 1 receptor ͑AT 1 R͒ is not well understood. Therefore, we investigated the cellular trafficking of AT 1 R-enhanced green fluorescent protein ͑EGFP͒ ͑AT 1 R-EGFP͒ heterologously expressed in HEK293 cells by determining the change in donor lifetime ͑AT 1 R-EGFP͒ in the presence or absence of acceptor͑s͒ using fluorescence lifetime imaging-fluorescence resonance energy transfer ͑FRET͒ microscopy. The average lifetime of AT 1 R-EGFP in our donor-alone samples was ϳ2.33 ns. The basal state lifetime was shortened slightly in the presence of Rab5 ͑2.01± 0.10 ns͒ or Rab7 ͑2.11± 0.11 ns͒ labeled with Alexa 555, as the acceptor fluorophore. A 5-min Ang II treatment markedly shortened the lifetime of AT 1 R-EGFP in the presence of Rab5-Alexa 555 ͑1.78± 0.31 ns͒ but was affected minimally in the presence of Rab7-Alexa 555 ͑2.09± 0.37 ns͒. A 30-min Ang II treatment further decreased the AT 1 R-EGFP lifetime in the presence of both Rab5-and Rab7-Alexa 555. Latrunculin A but not nocodazole pretreatment blocked the ability of Ang II to shorten the AT 1 R-EGFP lifetime. The occurrence of FRET between AT 1 R-EGFP ͑donor͒ and LAMP1-Alexa 555 ͑acceptor͒ with Ang II stimulation was impaired by photobleaching the acceptor. These studies demonstrate that Ang IIinduced AT 1 R lysosomal degradation through its association with LAMP1 is regulated by Rab5/7 via mechanisms that are dependent on intact actin cytoskeletons.

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“…The fluorophore pairs (Invitrogen, Life Technologies) used for FRET imaging were Alexa Fluor 555 (the acceptor dipole) conjugated with D 1 R antibody and pIR-Alexa Fluor 488 (the donor dipole). Seven images were acquired for each FRET analysis with an Olympus Fluoview FV300 laser scanning confocal microscope equipped with a ϫ60/1.4 NA objective, an Argon (488 nm) and HeNe (543 nm) laser, emission filters of 515/50 nm, and a 590-nm long pass filter (28).…”

Section: Förster Resonance Energy Transfer (Fret) Microscopymentioning

confidence: 99%

Sorting Nexin 5 and Dopamine D1 Receptor Regulate the Expression of the Insulin Receptor in Human Renal Proximal Tubule Cells

Yang

Jones

et al. 2015

Endocrinology

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Sorting nexin 5 (SNX5) belongs to the SNX family, which is composed of a diverse group of proteins that mediate trafficking of plasma membrane proteins, receptors, and transporters. SNX5 is important in the resensitization of the dopamine D1-like receptor (D1R). D1R is uncoupled from its effector proteins in hypertension and diabetes, and treatment of diabetes restores D1R function and insulin receptor (IR) expression. We tested the hypothesis that the D1R and SNX5 regulate IR by studying the expression, distribution, dynamics, and functional consequences of their interaction in human renal proximal tubule cells (hRPTCs). D1R, SNX5, and IR were expressed and colocalized in the brush border of RPTs. Insulin promoted the colocalization of SNX5 and IR at the perinuclear area of hRPTCs. Unlike SNX5, the D1R colocalized and coimmunoprecipitated with IR, and this interaction was enhanced by insulin. To evaluate the role of SNX5 and D1R on IR signaling, we silenced via RNA interference the endogenous expression of SNX5 or the D1R gene DRD1 in hRPTCs. We observed a decrease in IR expression and abundance of phosphorylated IR substrate and phosphorylated protein kinase B, which are crucial components of the IR signal transduction pathway. Our data indicate that SNX5 and D1R are necessary for normal IR expression and activity. It is conceivable that D1R and SNX5 may interact to increase the sensitivity to insulin via a positive regulation of IR and insulin signaling.

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Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

Cited by 51 publications

References 55 publications

Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury

Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury

Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

Sorting Nexin 5 and Dopamine D1 Receptor Regulate the Expression of the Insulin Receptor in Human Renal Proximal Tubule Cells

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