Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice

Villar, Van Anthony M.; Jones, John E.; Armando, Inés; Asico, Laureano D.; Escano, Crisanto; Lee, Hewang; Wang, Xiaoyan; Yu, Yang; Pascua-Crusan, Annabelle M.; Palmes-Saloma, Cynthia; Felder, Robin A.; José, Pedro A.

doi:10.1074/jbc.m112.428458

Cited by 30 publications

(61 citation statements)

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“…SNX1, SNX2, SNX4, SNX5, and SNX6 have been reported to bind to epidermal growth factor receptor, platelet-derived growth factor receptor, leptin receptor, and IR (15,32,33). We have also reported that the D 5 R signaling involves SNX1, whereas D 1 R signaling involves SNX5 (12,16). In a separate study, we found that SNX5 positively regulates the expression of the insulin degrading enzyme in hRPTCs and silencing of the SNX5 results in an increase in circulating insulin levels (our unpublished data).…”

Section: Discussionmentioning

confidence: 79%

“…SNX1, SNX2, and SNX4 have been reported to regulate the cellular trafficking of receptors for epidermal growth factor, insulin, plateletderived growth factor, and leptin (15). In addition, we found that the recycling of D 5 R and D 1 R is also regulated by SNX1 and SNX5, respectively (12,16). In a separate study, we found that SNX5 also positively regulates the expression and activity of the insulin degrading enzyme; selective renal silencing of SNX5 in Wistar-Kyoto rats increases the circulating insulin levels (our unpublished data).…”

mentioning

confidence: 84%

“…We have reported that SNX5 physically interacts with D 1 R and SNX5 is involved in D 1 R trafficking (12,16). Because the D 1 R physically Figure 6.…”

Section: Ir Expression In the D 1 R Gene Drd1 Shrna-transfected Hrptcsmentioning

confidence: 95%

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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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Section: Discussionmentioning

confidence: 79%

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confidence: 84%

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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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“…7). Agonistactivated D 1 Rs and D 5 Rs dimerize in renal epithelial cells (P. Yu and P. Jose, unpublished observations), and the impairment of one receptor results in the total absence of cAMP production in response to agonist stimulation (68,69), indicating a collaborative association between D 1 Rs and D 5 Rs. These receptors dimerize with ANG II type 2 receptors to cooperatively Fig.…”

Section: -Like Dopamine Receptor Interactions With and Regulationmentioning

confidence: 94%

“…2A). Treatment with fenoldopam redistributed some of the D 1 -like dopamine receptors to the submembrane area [we have previously reported that only around 50% of D 5 Rs internalized upon agonist activation (69)] and enhanced their colocalization with ␣ 1A -ARs. In a nonpathological section of the human kidney, all three receptors were expressed abundantly at the cytoplasm of proximal tubules, as indicated by the positive staining for the proximal tubule marker CD15, where the receptors colocalized strongly, and at the distal convoluted tubules (Fig.…”

Section: -Like Dopamine Receptors Interact With Thementioning

confidence: 98%

Dopamine D₁-like receptors regulate the α_1A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice

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Asico

Armando

et al. 2014

American Journal of Physiology-Renal Physiology

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The homeostatic control of blood pressure hinges upon the delicate balance between prohypertensinogenic and antihypertensinogenic systems. D₁-like dopamine receptors [dopamine D₁ and D₅ receptors (D₁Rs and D₅Rs, respectively)] and the α₁A-adrenergic receptor (α₁A-AR) are expressed in the renal proximal tubule and engender opposing effects on Na(+) transport, i.e., natriuresis (via D₁Rs and D5Rs) or antinatriuresis (via α₁A-ARs). We tested the hypothesis that the D₁R/D₅R regulates the α₁A-AR. D₁-like dopamine receptors coimmunoprecipitated, colocalized, and cofractionated with α₁A-ARs in lipid rafts in immortalized human renal proximal tubule cells. Long-term treatment with the D₁R/D₅R agonist fenoldopam resulted in decreased D₁R and D₅R expression but increased α₁A-AR abundance in the plasma membrane. Short-term fenoldopam treatment stimulated the translocation of Na(+)-K(+)-ATPase from the plasma membrane to the cytosol that was partially reversed by an α₁A-AR agonist, which by itself induced Na(+)-K(+)-ATPase translocation from the cytosol to the plasma membrane. The α₁A-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na(+)-K(+)-ATPase activity. To determine the interaction among D₁Rs, D₅Rs, and α₁A-ARs in vivo, we used phenylephrine and A610603 to decrease Na(+) excretion in several D1-like dopamine receptor knockout mouse strains. Phenylephrine and A61603 treatment resulted in a partial reduction of urinary Na(+) excretion in wild-type mice and its abolition in D1R knockout, D₅R knockout, and D₁R-D₅R double-knockout mice. Our results demonstrate the ability of the D₁-like dopamine receptors to regulate the expression and activity of α₁A-AR. Elucidating the intricacies of the interaction among these receptors is crucial for a better understanding of the crosstalk between anti- and pro-hypertensive systems.

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Elucidating the Role of Lipid Rafts on G Protein-Coupled Receptor Function in the Mouse Kidney: An In Vivo Approach

Asico

Rozyyev

Crusan

et al. 2020

Methods in Molecular Biology

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Numerous G protein-coupled receptors (GPCRs) and GPCR-signaling molecules reside in lipid rafts and thus, are inherently regulated in these microdomains. However, the limitations of current methods to investigate lipid raft biology and GPCR activity in situ have hindered the complete understanding of the molecular underpinnings of GPCR trafficking and signaling, especially in the whole organism. This book chapter details an innovative in vivo approach to study the crucial role of lipid rafts on the workings of GPCRs in the mouse kidney. This protocol involves the use of a modified mini osmotic pump to deliver an agent that selectively disrupts the lipid raft in the kidney.

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Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice

Cited by 30 publications

References 50 publications

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

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

Dopamine D₁-like receptors regulate the α_1A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice

Elucidating the Role of Lipid Rafts on G Protein-Coupled Receptor Function in the Mouse Kidney: An In Vivo Approach

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Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice

Cited by 30 publications

References 50 publications

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

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

Dopamine D1-like receptors regulate the α1A-adrenergic receptor in human renal proximal tubule cells and D1-like dopamine receptor knockout mice

Elucidating the Role of Lipid Rafts on G Protein-Coupled Receptor Function in the Mouse Kidney: An In Vivo Approach

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Dopamine D₁-like receptors regulate the α_1A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice