ArticleAmerican journal of physiology. Renal physiology2018
Kir5.1 regulates Nedd4-2-mediated ubiquitination of Kir4.1 in distal nephron.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Stimulation of basolateral calcium-sensing receptor inhibits Kir4.1/Kir5.1 in the mouse distal convoluted tubule.American journal of physiology. Renal physiology · 2026Article
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Kir5.1 regulates Kir4.2 expression and is a key component of the 50-pS inwardly rectifying potassium channel in basolateral membrane of mouse proximal tubules.American journal of physiology. Renal physiology · 2025Article
- mTORc2 in Distal Convoluted Tubule and Renal K + Excretion during High Dietary K + Intake.Journal of the American Society of Nephrology : JASN · 2024Article
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity.The Journal of cell biology · 2024Article
- Editorial: 30th anniversary of the molecular cloning and identification of the Na-Cl cotransporter, NCC.Frontiers in physiology · 2023Article
- Control of sodium and potassium homeostasis by renal distal convoluted tubules.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Regulation of distal tubule sodium transport: mechanisms and roles in homeostasis and pathophysiology.Pflugers Archiv : European journal of physiology · 2022Review
- Inwardly rectifying KAmerican journal of physiology. Cell physiology · 2022Review
- Does the early aldosterone-induced SGK1 play a role in early Kaliuresis?Physiological reports · 2022Article
- The effect of high-dietary KFrontiers in physiology · 2022Article
- ROMK channels are inhibited in the aldosterone-sensitive distal nephron of renal tubule Nedd4-2-deficient mice.American journal of physiology. Renal physiology · 2022Article
- The E3 ubiquitin-protein ligase Nedd4-2 regulates the sodium chloride cotransporter NCC but is not required for a potassium-induced reduction of NCC expression.Frontiers in physiology · 2022Article
- Role of collecting duct principal cell NOS1β in sodium and potassium homeostasis.Physiological reports · 2021Article
- Deletion of renal Nedd4-2 abolishes the effect of high KAmerican journal of physiology. Renal physiology · 2021Article
- Deletion of Kir5.1 abolishes the effect of high NaAmerican journal of physiology. Renal physiology · 2021Article
- Inwardly rectifying potassium channel 5.1: Structure, function, and possible roles in diseases.Genes & diseases · 2021Review
- Deletion of renal Nedd4-2 abolishes the effect of high sodium intake (HS) on Kir4.1, ENaC, and NCC and causes hypokalemia during high HS.American journal of physiology. Renal physiology · 2021Article
- Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule.Journal of the American Society of Nephrology : JASN · 2020Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
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Abstract
Kir4.1/5.1 heterotetramer participates in generating the negative cell membrane potential in distal convoluted tubule (DCT) and plays a critical role in determining the activity of Na-Cl cotransporter (NCC). Kir5.1 contains a phosphothreonine motif at its COOH terminus (AA249-252). Coimmunoprecipitation showed that Nedd4-2 was associated with Kir5.1 in HEK293 cells cotransfected with Kir5.1 or Kir4.1/Kir5.1. GST pull-down further confirmed the association between Nedd4-2 and Kir5.1. Ubiquitination assay showed that Nedd4-2 increased the ubiquitination of Kir4.1/Kir5.1 heterotetramer in the cells cotransfected with Kir4.1/Kir5.1, but it has no effect on Kir4.1 or Kir5.1 alone. Patch-clamp and Western blot also demonstrated that coexpression of Nedd4-2 but not Nedd4-1 decreased K currents and Kir4.1 expression in the cells cotransfected with Kir4.1 and Kir5.1. In contrast, Nedd4-2 fails to inhibit Kir4.1 in the absence of Kir5.1 or in the cells transfected with the inactivated form of Nedd4-2 (Nedd4-2C821A). Moreover, the mutation of TPVT motif in the COOH terminus of Kir5.1 largely abolished the association of Nedd4-2 with Kir5.1 and abolished the inhibitory effect of Nedd4-2 on K currents in HEK293 cells transfected with Kir4.1 and Kir5.1 mutant (Kir5.1T249A). Finally, the basolateral K conductance in the DCT and Kir4.1 expression is significantly increased in the kidney-specific Nedd4-2 knockout or in Kir5.1 knockout mice in comparison to their corresponding wild-type littermates. We conclude that Nedd4-2 binds to Kir5.1 at the phosphothreonine motif of the COOH terminus, and the association of Nedd4-2 with Kir5.1 facilitates the ubiquitination of Kir4.1, thereby regulating its plasma expression in the DCT.
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