The AE4 transporter mediates kidney acid-base sensing

Helga Vitzthum; M Koch; L Eckermann; S L Svendsen; P Berg; C A Hübner; C A Wagner; J Leipziger; C Meyer-Schwesinger; H Ehmke

doi:10.1038/s41467-023-38562-x

The AE4 transporter mediates kidney acid-base sensing

Helga Vitzthum, M Koch, L Eckermann, S L Svendsen, P Berg, C A Hübner, C A Wagner, J Leipziger, C Meyer-Schwesinger, H Ehmke

Institut for Biomedicin - Forskning og uddannelse, Skou-bygningen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

15 Citationer (Scopus)

Abstract

The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.

Originalsprog	Engelsk
Artikelnummer	3051
Tidsskrift	Nature Communications
Vol/bind	14
Nummer	1
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-023-38562-x
Status	Udgivet - dec. 2023

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10.1038/s41467-023-38562-xLicens: CC BY

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title = "The AE4 transporter mediates kidney acid-base sensing",

abstract = "The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.",

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author = "Helga Vitzthum and M Koch and L Eckermann and Svendsen, {S L} and P Berg and H{\"u}bner, {C A} and Wagner, {C A} and J Leipziger and C Meyer-Schwesinger and H Ehmke",

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AU - Vitzthum, Helga

AU - Koch, M

AU - Eckermann, L

AU - Svendsen, S L

AU - Berg, P

AU - Hübner, C A

AU - Wagner, C A

AU - Leipziger, J

AU - Meyer-Schwesinger, C

AU - Ehmke, H

PY - 2023/12

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N2 - The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.

AB - The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.

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KW - Animals

KW - Bicarbonates/metabolism

KW - Chloride-Bicarbonate Antiporters

KW - Kidney/metabolism

KW - Membrane Transport Proteins/genetics

KW - Mice

KW - Nephrons/metabolism

KW - Sulfate Transporters/metabolism

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JO - Nature Communications

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The AE4 transporter mediates kidney acid-base sensing

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