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Na+–sulfate cotransporter SLC13A1

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Abstract

Sulfate is essential for normal physiology. The kidney plays a major role in sulfate homeostasis. Sulfate is freely filtered and strongly reabsorbed in the proximal tubule. The apical membrane Na+–sulfate cotransporter NaS1 (SLC13A1) mediates sulfate (re)absorption across renal proximal tubule and small intestinal epithelia. NaS1 encodes a 595-amino acid (≈66 kDa) protein with 13 putative transmembrane domains. Its substrate preferences are sodium and sulfate, thiosulfate, and selenate, and its activity is inhibited by molybdate, selenate, tungstate, thiosulfate, succinate, and citrate. NaS1 is primarily expressed in the kidney (proximal tubule) and intestine (duodenum to colon). NaS1 expression is down-regulated in the renal cortex by high sulfate diet, hypothyroidism, vitamin D depletion, glucocorticoids, hypokalemia, metabolic acidosis, and NSAIDs and up-regulated by low sulfate diet, thyroid hormone, vitamin D supplementation, growth hormone, chronic renal failure, and during post-natal growth. Disruption of murine NaS1 gene leads to hyposulfatemia and hypersulfaturia, as well as changes in metabolism, growth, fecundity, behavior, gut physiology, and liver detoxification. This suggests that NaS1 is an important sulfate transporter and its disruption leads to perturbed sulfate homeostasis, which contributes to numerous pathophysiological conditions.

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Acknowledgments

Research in the author's laboratory has been supported by the Australian National Health and Medical Research Council, the Australian Research Council, the Cancer Council Queensland, and the University of Queensland.

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  1. School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, 4072, Australia

    Daniel Markovich

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Correspondence to Daniel Markovich.

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This article is published as part of the Special Issue on “Sodium-coupled transporters in health and disease.”

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Markovich, D. Na+–sulfate cotransporter SLC13A1. Pflugers Arch - Eur J Physiol 466, 131–137 (2014). https://doi.org/10.1007/s00424-013-1388-8

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