The AE4 transporter mediates kidney acid-base sensing
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The AE4 transporter mediates kidney acid-base sensing. / Vitzthum, H; Koch, M; Eckermann, L; Svendsen, S L; Berg, P; Hübner, C A; Leipziger, J; Meyer-Schwesinger, C; Ehmke, H.
in: NAT COMMUN, Jahrgang 14, Nr. 1, 26.05.2023, S. 3051.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The AE4 transporter mediates kidney acid-base sensing
AU - Vitzthum, H
AU - Koch, M
AU - Eckermann, L
AU - Svendsen, S L
AU - Berg, P
AU - Hübner, C A
AU - Leipziger, J
AU - Meyer-Schwesinger, C
AU - Ehmke, H
N1 - © 2023. The Author(s).
PY - 2023/5/26
Y1 - 2023/5/26
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.
KW - Mice
KW - Animals
KW - Kidney/metabolism
KW - Membrane Transport Proteins/genetics
KW - Acid-Base Equilibrium/physiology
KW - Nephrons/metabolism
KW - Sulfate Transporters/metabolism
KW - Bicarbonates/metabolism
KW - Chloride-Bicarbonate Antiporters
U2 - 10.1038/s41467-023-38562-x
DO - 10.1038/s41467-023-38562-x
M3 - SCORING: Journal article
C2 - 37236964
VL - 14
SP - 3051
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -