SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis

Ehud Ohana, Nikolay Shcheynikov, Orson W. Moe, Shmuel Muallem

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The combination of hyperoxaluria and hypocitraturia can trigger Ca 2+-oxalate stone formation, even in the absence of hypercalciuria, but the molecularmechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wildtypemice, Slc26a6-nullmice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. These findings reveal amolecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca2+-oxalate stone formation.

Original languageEnglish (US)
Pages (from-to)1617-1626
Number of pages10
JournalJournal of the American Society of Nephrology
Volume24
Issue number10
DOIs
StatePublished - Oct 2013

Fingerprint

Oxalates
Citric Acid
Homeostasis
Hyperoxaluria
Hypercalciuria
Succinic Acid
Xenopus
Oocytes
Sodium
Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis. / Ohana, Ehud; Shcheynikov, Nikolay; Moe, Orson W.; Muallem, Shmuel.

In: Journal of the American Society of Nephrology, Vol. 24, No. 10, 10.2013, p. 1617-1626.

Research output: Contribution to journalArticle

Ohana, Ehud ; Shcheynikov, Nikolay ; Moe, Orson W. ; Muallem, Shmuel. / SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis. In: Journal of the American Society of Nephrology. 2013 ; Vol. 24, No. 10. pp. 1617-1626.
@article{f3ae812b5a7a481bb6751700825fd796,
title = "SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis",
abstract = "The combination of hyperoxaluria and hypocitraturia can trigger Ca 2+-oxalate stone formation, even in the absence of hypercalciuria, but the molecularmechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wildtypemice, Slc26a6-nullmice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. These findings reveal amolecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca2+-oxalate stone formation.",
author = "Ehud Ohana and Nikolay Shcheynikov and Moe, {Orson W.} and Shmuel Muallem",
year = "2013",
month = "10",
doi = "10.1681/ASN.2013010080",
language = "English (US)",
volume = "24",
pages = "1617--1626",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "10",

}

TY - JOUR

T1 - SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis

AU - Ohana, Ehud

AU - Shcheynikov, Nikolay

AU - Moe, Orson W.

AU - Muallem, Shmuel

PY - 2013/10

Y1 - 2013/10

N2 - The combination of hyperoxaluria and hypocitraturia can trigger Ca 2+-oxalate stone formation, even in the absence of hypercalciuria, but the molecularmechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wildtypemice, Slc26a6-nullmice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. These findings reveal amolecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca2+-oxalate stone formation.

AB - The combination of hyperoxaluria and hypocitraturia can trigger Ca 2+-oxalate stone formation, even in the absence of hypercalciuria, but the molecularmechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wildtypemice, Slc26a6-nullmice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. These findings reveal amolecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca2+-oxalate stone formation.

UR - http://www.scopus.com/inward/record.url?scp=84885063137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885063137&partnerID=8YFLogxK

U2 - 10.1681/ASN.2013010080

DO - 10.1681/ASN.2013010080

M3 - Article

C2 - 23833257

AN - SCOPUS:84885063137

VL - 24

SP - 1617

EP - 1626

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 10

ER -