Skip to main content

Advertisement

Log in

One gene, two paracellular ion channels—claudin-10 in the kidney

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Claudins are tight junction membrane proteins and regulate the paracellular passage of ions and water. They can seal the paracellular cleft against solute passage but also form paracellular channels. They are tetraspan proteins with two extracellular segments. Claudin-10 exists in at least two functional isoforms, claudin-10a and claudin-10b, that differ in their first transmembrane segment and first extracellular segment. Both isoforms act as selective paracellular ion channels, either for anions (claudin-10a) or for cations (claudin-10b). Their diverse functions are reflected in completely different expression patterns in the body, especially in the kidney. Their structural and functional similarities and differences make them ideal subjects to study determinants of claudin charge selectivity and pore formation. This review aims to summarise research on permeability properties of the claudin-10 channels and their role in physiology and pathophysiology of the kidney.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Amasheh S, Meiri N, Gitter AH, Schoneberg T, Mankertz J, Schulzke JD, Fromm M (2002) Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 115:4969–4976

    Article  CAS  PubMed  Google Scholar 

  2. Amasheh S, Schmidt T, Mahn M, Florian P, Mankertz J, Tavalali S, Gitter AH, Schulzke JD, Fromm M (2005) Contribution of claudin-5 to barrier properties in tight junctions of epithelial cells. Cell Tissue Res 321:89–96

    Article  CAS  PubMed  Google Scholar 

  3. Angelow S, El-Husseini R, Kanzawa SA, Yu AS (2007) Renal localization and function of the tight junction protein, claudin-19. Am J Physiol Renal Physiol 293:F166–F177

    Article  CAS  PubMed  Google Scholar 

  4. Angelow S, Kim KJ, Yu AS (2006) Claudin-8 modulates paracellular permeability to acidic and basic ions in MDCK II cells. J Physiol 571:15–26

    Article  CAS  PubMed  Google Scholar 

  5. Barratt LJ, Rector FC Jr, Kokko JP, Seldin DW (1974) Factors governing the transepithelial potential difference across the proximal tubule of the rat kidney. J Clin Invest 53:454–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Breiderhoff T, Himmerkus N, Stuiver M, Mutig K, Will C, Meij IC, Bachmann S, Bleich M, Willnow TE, Müller D (2012) Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis. Proc Natl Acad Sci U S A 109:14241–14246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Colegio OR, Van Itallie CM, McCrea HJ, Rahner C, Anderson JM (2002) Claudins create charge-selective channels in the paracellular pathway between epithelial cells. Am J Physiol Cell Physiol 283:C142–C147

    Article  CAS  PubMed  Google Scholar 

  8. Conrad MP, Piontek J, Gunzel D, Fromm M, Krug SM (2016) Molecular basis of claudin-17 anion selectivity. Cell Mol Life Sci 73:185–200

    Article  CAS  PubMed  Google Scholar 

  9. Eisenman G (1962) Cation selective glass electrodes and their mode of operation. Biophys J 2:259–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Enck AH, Berger UV, Yu AS (2001) Claudin-2 is selectively expressed in proximal nephron in mouse kidney. Am J Physiol Renal Physiol 281:F966–F974

    Article  CAS  PubMed  Google Scholar 

  11. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Furuse M, Furuse K, Sasaki H, Tsukita S (2001) Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol 153:263–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 156:1099–1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, Hou J (2012) Claudin-14 regulates renal Ca(+)(+) transport in response to CaSR signalling via a novel microRNA pathway. EMBO J 31:1999–2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Günzel D, Stuiver M, Kausalya PJ, Haisch L, Krug SM, Rosenthal R, Meij IC, Hunziker W, Fromm M, Muller D (2009) Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function. J Cell Sci 122:1507–1517

    Article  PubMed  Google Scholar 

  16. Hou J, Renigunta A, Gomes AS, Hou M, Paul DL, Waldegger S, Goodenough DA (2009) Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium. Proc Natl Acad Sci U S A 106:15350–15355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hou J, Shan Q, Wang T, Gomes AS, Yan Q, Paul DL, Bleich M, Goodenough DA (2007) Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. J Biol Chem 282:17114–17122

    Article  CAS  PubMed  Google Scholar 

  18. Inai T, Kamimura T, Hirose E, Iida H, Shibata Y (2010) The protoplasmic or exoplasmic face association of tight junction particles cannot predict paracellular permeability or heterotypic claudin compatibility. Eur J Cell Biol 89:547–556

    Article  CAS  PubMed  Google Scholar 

  19. Inai T, Sengoku A, Guan X, Hirose E, Iida H, Shibata Y (2005) Heterogeneity in expression and subcellular localization of tight junction proteins, claudin-10 and -15, examined by RT-PCR and immunofluorescence microscopy. Arch Histol Cytol 68:349–360

    Article  CAS  PubMed  Google Scholar 

  20. Kirk A, Campbell S, Bass P, Mason J, Collins J (2010) Differential expression of claudin tight junction proteins in the human cortical nephron. Nephrol Dial Transplant 25:2107–2119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kiuchi-Saishin Y, Gotoh S, Furuse M, Takasuga A, Tano Y, Tsukita S (2002) Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments. J Am Soc Nephrol 13:875–886

    CAS  PubMed  Google Scholar 

  22. Konrad M, Schaller A, Seelow D, Pandey AV, Waldegger S, Lesslauer A, Vitzthum H, Suzuki Y, Luk JM, Becker C, Schlingmann KP, Schmid M, Rodriguez-Soriano J, Ariceta G, Cano F, Enriquez R, Juppner H, Bakkaloglu SA, Hediger MA, Gallati S, Neuhauss SC, Nurnberg P, Weber S (2006) Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement. Am J Hum Genet 79:949–957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Krug SM, Gunzel D, Conrad MP, Rosenthal R, Fromm A, Amasheh S, Schulzke JD, Fromm M (2012) Claudin-17 forms tight junction channels with distinct anion selectivity. Cell Mol Life Sci 69:2765–2778

    Article  CAS  PubMed  Google Scholar 

  24. Lee JW, Chou CL, Knepper MA (2015) Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J Am Soc Nephrol 26:2669–2677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lee NP, Tong MK, Leung PP, Chan VW, Leung S, Tam PC, Chan KW, Lee KF, Yeung WS, Luk JM (2006) Kidney claudin-19: localization in distal tubules and collecting ducts and dysregulation in polycystic renal disease. FEBS Lett 580:923–931

    Article  CAS  PubMed  Google Scholar 

  26. Li J, Angelow S, Linge A, Zhuo M, Yu AS (2013) Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteines. Am J Physiol Cell Physiol 305:C190–C196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Milatz S, Krug SM, Rosenthal R, Günzel D, Muller D, Schulzke JD, Amasheh S, Fromm M (2010) Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes. Biochim Biophys Acta 1798:2048–2057

    Article  CAS  PubMed  Google Scholar 

  28. Milatz S, Himmerkus N, Wulfmeyer VC, Drewell H, Mutig K, Hou J, Breiderhoff T, Müller D, Fromm M, Bleich M, Günzel D (2017) Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport. Proc Natl Acad Sci USA. (in press)

  29. Morita K, Furuse M, Fujimoto K, Tsukita S (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A 96:511–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Morita K, Sasaki H, Fujimoto K, Furuse M, Tsukita S (1999) Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. J Cell Biol 145:579–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161:653–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ohta H, Adachi H, Takiguchi M, Inaba M (2006) Restricted localization of claudin-16 at the tight junction in the thick ascending limb of Henle’s loop together with claudins 3, 4, and 10 in bovine nephrons. J Vet Med Sci 68:453–463

    Article  CAS  PubMed  Google Scholar 

  33. Plain A, Wulfmeyer VC, Milatz S, Klietz A, Hou J, Bleich M, Himmerkus N (2016) Corticomedullary difference in the effects of dietary Ca(2)(+) on tight junction properties in thick ascending limbs of Henle’s loop. Pflugers Arch 468:293–303

    Article  CAS  PubMed  Google Scholar 

  34. Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke JD, Amasheh S, Gunzel D, Fromm M (2010) Claudin-2, a component of the tight junction, forms a paracellular water channel. J Cell Sci 123:1913–1921

    Article  CAS  PubMed  Google Scholar 

  35. Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP (1999) Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285:103–106

    Article  CAS  PubMed  Google Scholar 

  36. Tanaka H, Yamamoto Y, Kashihara H, Yamazaki Y, Tani K, Fujiyoshi Y, Mineta K, Takeuchi K, Tamura A, Tsukita S (2016) Claudin-21 has a paracellular channel role at tight junctions. Mol Cell Biol 36:954–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Van Itallie C, Rahner C, Anderson JM (2001) Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 107:1319–1327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Van Itallie CM, Fanning AS, Anderson JM (2003) Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins. Am J Physiol Renal Physiol 285:F1078–F1084

    Article  CAS  PubMed  Google Scholar 

  39. Van Itallie CM, Rogan S, Yu A, Vidal LS, Holmes J, Anderson JM (2006) Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities. Am J Physiol Renal Physiol 291:F1288–F1299

    Article  CAS  PubMed  Google Scholar 

  40. Will C, Breiderhoff T, Thumfart J, Stuiver M, Kopplin K, Sommer K, Günzel D, Querfeld U, Meij IC, Shan Q, Bleich M, Willnow TE, Müller D (2010) Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting. Am J Physiol Renal Physiol 298:F1152–F1161

    Article  CAS  PubMed  Google Scholar 

  41. Wu J, Helftenbein G, Koslowski M, Sahin U, Tureci O (2006) Identification of new claudin family members by a novel PSI-BLAST based approach with enhanced specificity. Proteins 65:808–815

    Article  CAS  PubMed  Google Scholar 

  42. Yu AS, Cheng MH, Angelow S, Gunzel D, Kanzawa SA, Schneeberger EE, Fromm M, Coalson RD (2009) Molecular basis for cation selectivity in claudin-2-based paracellular pores: identification of an electrostatic interaction site. J Gen Physiol 133:111–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yu AS, Enck AH, Lencer WI, Schneeberger EE (2003) Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation. J Biol Chem 278:17350–17359

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Susanne Milatz.

Additional information

This article is published as part of the Special Issue on “Claudins – physiology, pathophysiology and clinical relevance”.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Milatz, S., Breiderhoff, T. One gene, two paracellular ion channels—claudin-10 in the kidney. Pflugers Arch - Eur J Physiol 469, 115–121 (2017). https://doi.org/10.1007/s00424-016-1921-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-016-1921-7

Keywords

Navigation