Dataset Information

Magnesium and Calcium Homeostasis Depend on KCTD1 Function in the Distal Nephron.

ABSTRACT: Magnesium (Mg²⁺) homeostasis depends on active transcellular Mg²⁺ reuptake from urine in distal convoluted tubules (DCTs) via the Mg²⁺ channel TRPM6, whose activity has been proposed to be regulated by EGF. Calcium (Ca²⁺) homeostasis depends on paracellular reabsorption in the thick ascending limbs of Henle (TALs). KCTD1 promotes terminal differentiation of TALs/DCTs, but how its deficiency affects urinary Mg²⁺ and Ca²⁺ reabsorption is unknown. Here, this study shows that DCT1-specific KCTD1 inactivation leads to hypomagnesemia despite normal TRPM6 levels because of reduced levels of the sodium chloride co-transporter NCC, whereas Mg²⁺ homeostasis does not depend on EGF. Moreover, KCTD1 deficiency impairs paracellular urinary Ca²⁺ and Mg²⁺ reabsorption in TALs because of reduced NKCC2/claudin-16/-19 and increased claudin-14 expression, leading to hypocalcemia and consequently to secondary hyperparathyroidism and progressive metabolic bone disease. Thus, KCTD1 regulates urinary reabsorption of Mg²⁺ and Ca²⁺ by inducing expression of NCC in DCTs and NKCC2/claudin-16/-19 in TALs.

SUBMITTER: Marneros AG

PROVIDER: S-EPMC7869691 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Magnesium and Calcium Homeostasis Depend on KCTD1 Function in the Distal Nephron.

Marneros Alexander G AG

Cell reports 20210101 2

Magnesium (Mg2+) homeostasis depends on active transcellular Mg2+ reuptake from urine in distal convoluted tubules (DCTs) via the Mg2+ channel TRPM6, whose activity has been proposed to be regulated by EGF. Calcium (Ca2+) homeostasis depends on paracellular reabsorption in the thick ascending limbs of Henle (TALs). KCTD1 promotes terminal differentiation of TALs/DCTs, but how its deficiency affects urinary Mg2+ and Ca2+ reabsorpti ...[more]

PMID: 33440155

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Dataset Information

Magnesium and Calcium Homeostasis Depend on KCTD1 Function in the Distal Nephron.

Publications

Magnesium and Calcium Homeostasis Depend on KCTD1 Function in the Distal Nephron.

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