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The SLC14 gene family of urea transporters

  • The ABC of Solute Carriers
  • Guest Editor: Matthias A. Hediger
  • Published:
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Abstract

Carrier-mediated urea transport allows rapid urea movement across the cell membrane, which is particularly important in the process of urinary concentration and for rapid urea equilibrium in non-renal tissues. Urea transporters mediate passive urea uptake that is inhibited by phloretin and urea analogues. Facilitated urea transporters are divided into two classes: (1) the renal tubular/testicular type of urea transporter, UT-A1 to -A5, encoded by alternative splicing of the SLC14A2 gene, and (2) the erythrocyte urea transporter UT-B1 encoded by the SLC14A1 gene. The primary structure of urea transporters is unique, consisting of two extended, hydrophobic, membrane-spanning domains and an extracellular glycosylated-connecting loop. UT-A1 is the result of a gene duplication of this two-halves-structure, and the duplicated portions are linked together by a large intracellular hydrophilic loop, carrying several putative protein kinase A (PKA) and -C (PKC) phosphorylation sites. UT-A1 is located in the apical membrane of the kidney inner medullary collecting duct cells, where it is stimulated acutely by cAMP-mediated phosphorylation in response to the antidiuretic hormone vasopressin. Vasopressin also up-regulates UT-A2 mRNA/protein expression in the descending thin limb of the loops of Henle. UT-A1 and UT-A2 are regulated independently and respond differently to changes in dietary protein content. UT-A3 and UT-A4 are located in the rat kidney medulla and UT-A5 in the mouse testis. The widely expressed UT-B participates in urea recycling in the descending vasa recta, as demonstrated by a relatively mild "urea-selective" urinary concentrating defect in transgenic UT-B null mice and individuals with the Jknull blood group.

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Acknowledgements

Since this review is restricted to the discussion of the mammalian urea transporters, we regret the omission of mentioning the identifiable homologues in frog [6] and several types of fish [19, 20, 30, 47, 53, 54]. We also apologize for the omission of many excellent reviews and references due to space limitations. CS is supported by grants from Thai Research Foundation and Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand.

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  1. Renal Unit, Department of Medicine, Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand

    Chairat Shayakul

  2. Membrane Biology Program, Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA

    Matthias A. Hediger

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  1. Chairat Shayakul
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Shayakul, C., Hediger, M.A. The SLC14 gene family of urea transporters. Pflugers Arch - Eur J Physiol 447, 603–609 (2004). https://doi.org/10.1007/s00424-003-1124-x

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