Skip to main content

Advertisement

SpringerLink
Log in

Claudins in renal physiology and disease

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The tight junction forms the paracellular permeability barrier in all epithelia, including the renal tubule. Claudins are a family of tight junction membrane proteins with four transmembrane domains that form the paracellular pore and barrier. Their first extracellular domain appears to be important for determining selectivity. A number of claudin isoforms have been found to be important in renal tubule function, both in adults and in neonates. Familial hypomagnesemic hypercalciuria with nephrocalcinosis is an autosomal recessive syndrome characterized by impaired reabsorption of Mg and Ca in the thick ascending limb of Henle's loop. Mutations in claudin-16 and 19 can both cause this syndrome, but the pathophysiological mechanism remains controversial.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Rector FC Jr, Martinez-Maldonado M, Brunner FP, Seldin DW (1966) Evidence for passive reabsorption of NaCl in proximal tubule of rat kidney. J Clin Invest 45:1060–1070

    Google Scholar 

  2. Berry CA, Rector FC Jr (1991) Mechanism of proximal NaCl reabsorption in the proximal tubule of the mammalian kidney. Semin Nephrol 11:86–97

    CAS  PubMed  Google Scholar 

  3. Quigley R, Baum M (2002) Developmental changes in rabbit proximal straight tubule paracellular permeability. Am J Physiol Ren Physiol 283:F525–F531

    CAS  Google Scholar 

  4. Shah M, Quigley R, Baum M (1998) Maturation of rabbit proximal straight tubule chloride/base exchange. Am J Physiol 274:F883–F888

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hebert SC, Andreoli TE (1984) Control of NaCl transport in the thick ascending limb. Am J Physiol 246:F745–F756

    CAS  PubMed  Google Scholar 

  6. Ussing HH, Windhager EE (1964) Nature of shunt path and active solute transport path through frog skin epithelium. Acta Physiol Scand 61:484–504

    CAS  PubMed  Google Scholar 

  7. Machen TE, Erlij D, Wooding FB (1972) Permeable junctional complexes. The movement of lanthanum across rabbit gallbladder and intestine. J Cell Biol 54:302–312

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Gonzalez-Mariscal L, Tapia R, Chamorro D (2008) Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta 1778:729–756

    CAS  PubMed  Google Scholar 

  9. Angelow S, Yu AS (2007) Claudins and paracellular transport: an update. Curr Opin Nephrol Hypertens 16:459–464

    CAS  PubMed  Google Scholar 

  10. McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Skare IB, Lynch RD, Schneeberger EE (2000) Inducible expression of claudin-1-myc but not occludin-VSV-G results in aberrant tight junction strand formation in MDCK cells. J Cell Sci 113(Pt 19):3387–3398

    CAS  PubMed  Google Scholar 

  11. 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 Ren Physiol 285:F1078–F1084

    Google Scholar 

  12. Wen H, Watry DD, Marcondes MC, Fox HS (2004) Selective decrease in paracellular conductance of tight junctions: role of the first extracellular domain of claudin-5. Mol Cell Biol 24:8408–8417

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 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

    CAS  PubMed  Google Scholar 

  14. Nakano Y, Kim SH, Kim HM, Sanneman JD, Zhang Y, Smith RJ, Marcus DC, Wangemann P, Nessler RA, Banfi B (2009) A claudin-9-based ion permeability barrier is essential for hearing. PLoS Genet 5:e1000610

    PubMed  PubMed Central  Google Scholar 

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

    CAS  Google Scholar 

  16. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hou J, Paul DL, Goodenough DA (2005) Paracellin-1 and the modulation of ion selectivity of tight junctions. J Cell Sci 118:5109–5118

    CAS  PubMed  Google Scholar 

  18. Muto S, Hata M, Taniguchi J, Tsuruoka S, Moriwaki K, Saitou M, Furuse K, Sasaki H, Fujimura A, Imai M, Kusano E, Tsukita S, Furuse M (2010) Claudin-2-deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules. Proc Natl Acad Sci USA 107:8011–8016

    CAS  PubMed  Google Scholar 

  19. Colegio OR, Van Itallie C, Rahner C, Anderson JM (2003) Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture. Am J Physiol Cell Physiol 284:C1346–C1354

    CAS  PubMed  Google Scholar 

  20. 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

    CAS  PubMed  Google Scholar 

  21. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Van Itallie CM, Holmes J, Bridges A, Gookin JL, Coccaro MR, Proctor W, Colegio OR, Anderson JM (2008) The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci 121:298–305

    PubMed  Google Scholar 

  23. Angelow S, Yu AS (2009) Cysteine mutagenesis to study the structure of claudin-2 paracellular pores. Ann NY Acad Sci 1165:143–147

    CAS  PubMed  Google Scholar 

  24. Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG (2000) Hypomagnesaemia-hypercalciuria-nephrocalcinosis: a report of nine cases and a review. Nephrol Dial Transplant 15:605–610

    CAS  PubMed  Google Scholar 

  25. Manz F, Scharer K, Janka P, Lombeck J (1978) Renal magnesium wasting, incomplete tubular acidosis, hypercalciuria and nephrocalcinosis in siblings. Eur J Pediatr 128:67–79

    CAS  PubMed  Google Scholar 

  26. Kari JA, Farouq M, Alshaya HO (2003) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Pediatr Nephrol 18:506–510

    PubMed  Google Scholar 

  27. Kuwertz-Broking E, Frund S, Bulla M, Kleta R, August C, Kisters K (2001) Familial hypomagnesemia-hypercalciuria in 2 siblings. Clin Nephrol 56:155–161

    CAS  PubMed  Google Scholar 

  28. Martin Aguado M, Canals Baeza A, Sanguino Lopez L, Gavilan Martin C, Flores Serrano J (2001) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. An Esp Pediatr 54:174–177

    CAS  PubMed  Google Scholar 

  29. Mourani C, Khallouf E, Akkari V, Akatcherian C, Cochat P (1999) Early hypomagnesemia, hypercalciuria and nephrocalcinosis: two cases in a family. Arch Pediatr 6:748–751

    CAS  PubMed  Google Scholar 

  30. Evans RA, Carter JN, George CR, Walls RS, Newland RC, McDonnell GD, Lawrence JR (1981) The congenital “magnesium-losing kidney”. Report of two patients. Q J Med 50:39–52

    CAS  PubMed  Google Scholar 

  31. Praga M, Vara J, Gonzalez-Parra E, Andres A, Alamo C, Araque A, Ortiz A, Rodicio JL (1995) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Kidney Int 47:1419–1425

    CAS  PubMed  Google Scholar 

  32. Michelis MF, Drash AL, Linarelli LG, De Rubertis FR, Davis BB (1972) Decreased bicarbonate threshold and renal magnesium wasting in a sibship with distal renal tubular acidosis. (Evaluation of the pathophysiological role of parathyroid hormone). Metabolism 21:905–920

    CAS  PubMed  Google Scholar 

  33. Weber S, Schneider L, Peters M, Misselwitz J, Ronnefarth G, Boswald M, Bonzel KE, Seeman T, Sulakova T, Kuwertz-Broking E, Gregoric A, Palcoux JB, Tasic V, Manz F, Scharer K, Seyberth HW, Konrad M (2001) Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 12:1872–1881

    CAS  PubMed  Google Scholar 

  34. Cole DE, Quamme GA (2000) Inherited disorders of renal magnesium handling. J Am Soc Nephrol 11:1937–1947

    CAS  PubMed  Google Scholar 

  35. Torralbo A, Pina E, Portoles J, Sanchez-Fructuoso A, Barrientos A (1995) Renal magnesium wasting with hypercalciuria, nephrocalcinosis and ocular disorders. Nephron 69:472–475

    CAS  PubMed  Google Scholar 

  36. 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

    CAS  PubMed  Google Scholar 

  37. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 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

    CAS  PubMed  Google Scholar 

  39. Hou J, Renigunta A, Konrad M, Gomes AS, Schneeberger EE, Paul DL, Waldegger S, Goodenough DA (2008) Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest 118:619–628

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Rodriguez-Soriano J, Vallo A, Garcia-Fuentes M (1987) Hypomagnesaemia of hereditary renal origin. Pediatr Nephrol 1:465–472

    CAS  PubMed  Google Scholar 

  41. Blanchard A, Jeunemaitre X, Coudol P, Dechaux M, Froissart M, May A, Demontis R, Fournier A, Paillard M, Houillier P (2001) Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle. Kidney Int 59:2206–2215

    CAS  PubMed  Google Scholar 

  42. Burg MB, Green N (1973) Function of the thick ascending limb of Henle's loop. Am J Physiol 224:659–668

    CAS  PubMed  Google Scholar 

  43. Greger R (1981) Cation selectivity of the isolated perfused cortical thick ascending limb of Henle's loop of rabbit kidney. Pflugers Arch 390:30–37

    CAS  PubMed  Google Scholar 

  44. Burg M, Good D (1983) Sodium chloride coupled transport in mammalian nephrons. Annu Rev Physiol 45:533–547

    CAS  PubMed  Google Scholar 

  45. Ikari A, Matsumoto S, Harada H, Takagi K, Hayashi H, Suzuki Y, Degawa M, Miwa M (2006) Phosphorylation of paracellin-1 at Ser217 by protein kinase A is essential for localization in tight junctions. J Cell Sci 119:1781–1789

    CAS  PubMed  Google Scholar 

  46. Kausalya PJ, Amasheh S, Gunzel D, Wurps H, Muller D, Fromm M, Hunziker W (2006) Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16. J Clin Invest 116:878–891

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Thorleifsson G, Holm H, Edvardsson V, Walters GB, Styrkarsdottir U, Gudbjartsson DF, Sulem P, Halldorsson BV, de Vegt F, d'Ancona FC, den Heijer M, Franzson L, Christiansen C, Alexandersen P, Rafnar T, Kristjansson K, Sigurdsson G, Kiemeney LA, Bodvarsson M, Indridason OS, Palsson R, Kong A, Thorsteinsdottir U, Stefansson K (2009) Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nat Genet 41:926–930

    CAS  PubMed  Google Scholar 

  48. Ben-Yosef T, Belyantseva IA, Saunders TL, Hughes ED, Kawamoto K, Van Itallie CM, Beyer LA, Halsey K, Gardner DJ, Wilcox ER, Rasmussen J, Anderson JM, Dolan DF, Forge A, Raphael Y, Camper SA, Friedman TB (2003) Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration. Hum Mol Genet 12:2049–2061

    CAS  PubMed  Google Scholar 

  49. Elkouby-Naor L, Abassi Z, Lagziel A, Gow A, Ben-Yosef T (2008) Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins. Cell Tissue Res 333:427–438

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  Google Scholar 

  51. 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 

  52. 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

    CAS  PubMed  Google Scholar 

  53. 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

    CAS  PubMed  Google Scholar 

  54. Li WY, Huey CL, Yu AS (2004) Expression of claudin-7 and -8 along the mouse nephron. Am J Physiol Ren Physiol 286:F1063–F1071

    CAS  Google Scholar 

  55. Alexandre MD, Lu Q, Chen YH (2005) Overexpression of claudin-7 decreases the paracellular Cl- conductance and increases the paracellular Na + conductance in LLC-PK1 cells. J Cell Sci 118:2683–2693

    CAS  PubMed  Google Scholar 

  56. Hou J, Gomes AS, Paul DL, Goodenough DA (2006) Study of claudin function by RNA interference. J Biol Chem 281:36117–36123

    CAS  PubMed  Google Scholar 

  57. Tatum R, Zhang Y, Salleng K, Lu Z, Lin JJ, Lu Q, Jeansonne BG, Ding L, Chen YH (2010) Renal salt wasting and chronic dehydration in claudin-7-deficient mice. Am J Physiol Ren Physiol 298:F24–F34

    CAS  Google Scholar 

  58. Abuazza G, Becker A, Williams SS, Chakravarty S, Truong HT, Lin F, Baum M (2006) Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins. Am J Physiol Ren Physiol 291:F1132–F1141

    CAS  Google Scholar 

  59. Sas D, Hu M, Moe OW, Baum M (2008) Effect of claudins 6 and 9 on paracellular permeability in MDCK II cells. Am J Physiol Regul Integr Comp Physiol 295:R1713–R1719

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Wittchen ES, Haskins J, Stevenson BR (1999) Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3. J Biol Chem 274:35179–35185

    CAS  PubMed  Google Scholar 

  61. Van Itallie CM, Gambling TM, Carson JL, Anderson JM (2005) Palmitoylation of claudins is required for efficient tight-junction localization. J Cell Sci 118:1427–1436

    PubMed  Google Scholar 

  62. Muller D, Kausalya PJ, Claverie-Martin F, Meij IC, Eggert P, Garcia-Nieto V, Hunziker W (2003) A novel claudin 16 mutation associated with childhood hypercalciuria abolishes binding to ZO-1 and results in lysosomal mistargeting. Am J Hum Genet 73:1293–1301

    PubMed  PubMed Central  Google Scholar 

  63. Angelow S, Ahlstrom R, Yu AS (2008) Biology of claudins. Am J Physiol Ren Physiol 295:F867–F876

    CAS  Google Scholar 

  64. Inai T, Kobayashi J, Shibata Y (1999) Claudin-1 contributes to the epithelial barrier function in MDCK cells. Eur J Cell Biol 78:849–855

    CAS  PubMed  Google Scholar 

  65. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wolk B, Hatziioannou T, McKeating JA, Bieniasz PD, Rice CM (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446:801–805

    CAS  PubMed  Google Scholar 

  67. Meertens L, Bertaux C, Cukierman L, Cormier E, Lavillette D, Cosset FL, Dragic T (2008) The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J Virol 82:3555–3560

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56:61–72

    CAS  PubMed  Google Scholar 

  69. Morin PJ (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65:9603–9606

    CAS  PubMed  Google Scholar 

  70. Fujita K, Katahira J, Horiguchi Y, Sonoda N, Furuse M, Tsukita S (2000) Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein. FEBS Lett 476:258–261

    CAS  PubMed  Google Scholar 

  71. Sonoda N, Furuse M, Sasaki H, Yonemura S, Katahira J, Horiguchi Y, Tsukita S (1999) Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: evidence for direct involvement of claudins in tight junction barrier. J Cell Biol 147:195–204

    PubMed  PubMed Central  Google Scholar 

  72. 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

    PubMed  PubMed Central  Google Scholar 

  73. Hou J, Renigunta A, Yang J, Waldegger S (2010) Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci USA 107:18010–18015

    CAS  PubMed  Google Scholar 

  74. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhang J, Piontek J, Wolburg H, Piehl C, Liss M, Otten C, Christ A, Willnow TE, Blasig IE, Abdelilah-Seyfried S (2010) Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion. Proc Natl Acad Sci USA 107:1425–1430

    CAS  PubMed  Google Scholar 

  76. 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 Ren Physiol 291:F1288–F1299

    Google Scholar 

  77. Van Itallie C, Fanning AS, Anderson JM (2003) Reversal of charge selectivity in cation or anion selective epithelial lines by expression of different claudins. Am J Physiol Cell Physiol 286:F1078–F1084

    Google Scholar 

  78. Gow A, Southwood CM, Li JS, Pariali M, Riordan GP, Brodie SE, Danias J, Bronstein JM, Kachar B, Lazzarini RA (1999) CNS myelin and Sertoli cell tight junction strands are absent in Osp/claudin-11 null mice. Cell 99:649–659

    CAS  PubMed  Google Scholar 

  79. Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, Yamamoto Y, Wada T, Kojima T, Yokozaki H, Yamashita T, Kato S, Sawada N, Chiba H (2008) Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell 19:1912–1921

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Wilcox ER, Burton QL, Naz S, Riazuddin S, Smith TN, Ploplis B, Belyantseva I, Ben-Yosef T, Liburd NA, Morell RJ, Kachar B, Wu DK, Griffith AJ, Friedman TB (2001) Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 104:165–172

    CAS  PubMed  Google Scholar 

  81. 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 USA 106:15350–15355

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, University of Southern California, 2025 Zonal Avenue, RMR 406, Los Angeles, CA, 90089, USA

    Wanwarat Ananthapanyasut & Alan S. L. Yu

  2. Systems Biology and Disease Program, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA

    Jiahua Li & Alan S. L. Yu

Authors
  1. Jiahua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanwarat Ananthapanyasut
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan S. L. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alan S. L. Yu.

Additional information

Answers

1. B

2. D

3. A

4. E

5. E

6. C

Multiple choice questions (answers appear following the reference list)

Multiple choice questions (answers appear following the reference list)

  1. 1:

    Which of the following best describes paracellular permeability and transport in the late proximal tubule?

    1. A.

      The proximal tubule has a high transepithelial resistance and acts as a barrier to small ions.

    2. B.

      NaCl is reabsorbed paracellularly, driven by the Cl concentration gradient.

    3. C.

      Organic anions are secreted across the paracellular pathway.

    4. D.

      Water is predominantly reabsorbed via the paracellular pathway, driven by the osmotic gradient.

    5. E.

      The proximal tubule is selectively permeable to bicarbonate which is reabsorbed paracellularly.

  2. 2:

    Which domain of the claudin protein forms the lining of the paracellular pore?

    1. A.

      Amino terminal

    2. B.

      Carboxy terminal

    3. C.

      1st transmembrane domain

    4. D.

      1st extracellular domain

    5. E.

      Cytosolic loop between 2nd and 3rd transmembrane domain

  3. 3:

    It has been shown that D65 (aspartate residue at position 65) in claudin-2 is a cation-binding site that is responsible for its cation-selectivity. Which of the following mutation of claudin-2 would be most likely to turn claudin-2 from a cation-selective pore to an anion-selective pore?

    1. A.

      D65K (mutation to lysine)

    2. B.

      D65C (mutation to cysteine)

    3. C.

      D65A (mutation to alanine)

    4. D.

      D65S (mutation to serine)

    5. E.

      D65L (mutation to leucine)

  4. 4:

    All of the following are clinical features of familial hypomagnesemic hypercalciuria with nephrocalcinosis (FHHNC), EXCEPT:

    1. A.

      Increased fractional excretion of Mg

    2. B.

      Rickets

    3. C.

      Decreased GFR

    4. D.

      Ocular abnormalities

    5. E.

      Deafness

  5. 5:

    Which of the following treatments ameliorate the urinary Mg and Ca wasting in FHHNC?

    1. A.

      Thiazide diuretics

    2. B.

      Magnesium supplementation

    3. C.

      Amiloride

    4. D.

      Oral phosphate binders

    5. E.

      Kidney transplantation

  6. 6:

    Which of the following claudins are selectively expressed in the neonatal kidney but not in adult kidney?

    1. A.

      Claudin-2

    2. B.

      Claudin-7

    3. C.

      Claudin-9

    4. D.

      Claudin-16

    5. E.

      Claudin-19

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, J., Ananthapanyasut, W. & Yu, A.S.L. Claudins in renal physiology and disease. Pediatr Nephrol 26, 2133–2142 (2011). https://doi.org/10.1007/s00467-011-1824-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-011-1824-y

Keywords

Search

Navigation