Skip to main content
SpringerLink
Log in

Modulation of Intestinal Disorders by Claudin-2 and Occludin Via Canonical and Noncanonical Mechanisms

  • Chapter
  • First Online:
Tight Junctions

Abstract

The past 35 years, beginning with the identification of ZO-1 in 1986, have been an exciting time during which critical tight junction proteins were discovered. We have, however, only begun to define the mechanism by which tight junctions are regulated, their impact on health and disease, and noncanonical functions of individual tight junction-associated proteins. Here, we provide an overview of advances in understanding mechanisms of tight junction barrier regulation within the intestinal epithelium and discuss recent discoveries related to claudin-2 and occludin in greater detail. We anticipate that the next 35 years will yield major advances in fundamental understanding of tight junction protein interactions, regulation, and canonical and noncanonical functions that result in translational applications in which tight junction modulation is established as a therapeutic approach.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CK2:

Casein kinase 2

DSS:

Dextran sulfate sodium

FRAP:

Fluorescence recovery after photobleaching

MLC:

Myosin II regulatory light chain

MLCK:

Myosin light -chain kinase

TER:

Transepithelial electrical resistance

TNBS:

Trinitrobenzenesulfonic acid

TNF:

Tumor necrosis factor

References

  1. Farquhar M, Palade G (1963) Junctional complexes in various epithelia. J Cell Biol 17 (2):375-412

    Article  CAS  Google Scholar 

  2. Ussing HH, Windhager EE (1964) Nature of Shunt Path and Active Sodium Transport Path through Frog Skin Epithelium. Acta Physiol Scand 61:484-504

    CAS  PubMed  Google Scholar 

  3. Wade JB, Karnovsky MJ (1974) Fracture faces of osmotically disrupted zonulae occludentes. J Cell Biol 62 (2):344-350. https://doi.org/10.1083/jcb.62.2.344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Montesano R, Gabbiani G, Perrelet A, Orci L (1976) In vivo induction of tight junction proliferation in rat liver. J Cell Biol 68 (3):793-798. https://doi.org/10.1083/jcb.68.3.793

    Article  CAS  PubMed  Google Scholar 

  5. Bentzel CJ, Hainau B, Edelman A, Anagnostopoulos T, Benedetti EL (1976) Effect of plant cytokinins on microfilaments and tight junction permeability. Nature 264 (5587):666-668. https://doi.org/10.1038/264666a0

    Article  CAS  PubMed  Google Scholar 

  6. Madara JL, Pappenheimer JR (1987) Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J Membr Biol 100 (2):149-164

    Article  CAS  Google Scholar 

  7. Pappenheimer JR (1987) Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and hamsters. J Membr Biol 100 (2):137-148

    Article  CAS  Google Scholar 

  8. Pappenheimer JR, Reiss KZ (1987) Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol 100 (1):123-136. https://doi.org/10.1007/bf02209145

    Article  CAS  PubMed  Google Scholar 

  9. Meddings JB, Westergaard H (1989) Intestinal glucose transport using perfused rat jejunum in vivo: model analysis and derivation of corrected kinetic constants. Clin Sci (Lond) 76 (4):403-413. https://doi.org/10.1042/cs0760403

    Article  CAS  Google Scholar 

  10. Atisook K, Carlson S, Madara JL (1990) Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia. Am J Physiol 258 (1 Pt 1):C77-85. https://doi.org/10.1152/ajpcell.1990.258.1.C77

    Article  CAS  PubMed  Google Scholar 

  11. Turner JR, Madara JL (1995) Physiological regulation of intestinal epithelial tight junctions as a consequence of Na+-coupled nutrient transport. Gastroenterol 109 (4):1391-1396

    Article  CAS  Google Scholar 

  12. Uhing MR, Arango V (1997) Intestinal absorption of proline and leucine in chronically catheterized rats. Gastroenterol 113 (3):865-874

    Article  CAS  Google Scholar 

  13. Schwartz RM, Furne JK, Levitt MD (1995) Paracellular intestinal transport of six-carbon sugars is negligible in the rat. Gastroenterol 109 (4):1206-1213

    Article  CAS  Google Scholar 

  14. Fine KD, Ana CAS, Porter JL, Fordtran JS (1994) Mechanism by Which Glucose Stimulates the Passive Absorption of Small Solutes by the Human Jejunum in-Vivo. Gastroenterol 107 (2):389-395

    Article  CAS  Google Scholar 

  15. Fine KD, Santa Ana CA, Porter JL, Fordtran JS (1993) Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo. Gastroenterol 105 (4):1117-1125

    Article  CAS  Google Scholar 

  16. Turner JR, Cohen DE, Mrsny RJ, Madara JL (2000) Noninvasive in vivo analysis of human small intestinal paracellular absorption: regulation by Na+-glucose cotransport. Dig Dis Sci 45 (11):2122-2126. https://doi.org/10.1023/a:1026682900586

    Article  CAS  PubMed  Google Scholar 

  17. Pappenheimer JR (1998) Scaling of dimensions of small intestines in non-ruminant eutherian mammals and its significance for absorptive mechanisms. Comp Biochem Physiol A Mol Integr Physiol 121 (1):45-58.

    Article  CAS  Google Scholar 

  18. Karlsson J, Ungell A, Grasjo J, Artursson P (1999) Paracellular drug transport across intestinal epithelia: influence of charge and induced water flux. Eur J Pharm Sci 9 (1):47-56

    Article  CAS  Google Scholar 

  19. Berglund JJ, Riegler M, Zolotarevsky Y, Wenzl E, Turner JR (2001) Regulation of human jejunal transmucosal resistance and MLC phosphorylation by Na(+)-glucose cotransport. Am J Physiol - Gastrointest Liver Physiol 281 (6):G1487-1493. https://doi.org/10.1152/ajpgi.2001.281.6.G1487

    Article  CAS  PubMed  Google Scholar 

  20. Fihn BM, Sjoqvist A, Jodal M (2000) Permeability of the rat small intestinal epithelium along the villus-crypt axis: effects of glucose transport. Gastroenterol 119 (4):1029-1036. https://doi.org/10.1053/gast.2000.18148

    Article  CAS  Google Scholar 

  21. Pei L, Solis G, Nguyen MT, Kamat N, Magenheimer L, Zhuo M, Li J, Curry J, McDonough AA, Fields TA, Welch WJ, Yu AS (2016) Paracellular epithelial sodium transport maximizes energy efficiency in the kidney. J Clin Invest 126 (7):2509-2518. https://doi.org/10.1172/JCI83942

    Article  PubMed  PubMed Central  Google Scholar 

  22. Larsen EH, Mobjerg N (2006) Na+ recirculation and isosmotic transport. J Membr Biol 212 (1):1-15. https://doi.org/10.1007/s00232-006-0864-x

    Article  CAS  PubMed  Google Scholar 

  23. Turner JR, Rill BK, Carlson SL, Carnes D, Kerner R, Mrsny RJ, Madara JL (1997) Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol 273 (4):C1378-1385. https://doi.org/10.1152/ajpcell.1997.273.4.C1378

    Article  CAS  PubMed  Google Scholar 

  24. Taylor CT, Dzus AL, Colgan SP (1998) Autocrine regulation of epithelial permeability by hypoxia: role for polarized release of tumor necrosis factor alpha. Gastroenterol 114 (4):657-668

    Article  CAS  Google Scholar 

  25. Marano CW, Lewis SA, Garulacan LA, Soler AP, Mullin JM (1998) Tumor necrosis factor-alpha increases sodium and chloride conductance across the tight junction of CACO-2 BBE, a human intestinal epithelial cell line. J Membr Biol 161 (3):263-274

    Article  CAS  Google Scholar 

  26. Rodriguez P, Heyman M, Candalh C, Blaton MA, Bouchaud C (1995) Tumour necrosis factor-alpha induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers. Cytokine 7 (5):441-448. https://doi.org/10.1006/cyto.1995.0060

    Article  CAS  PubMed  Google Scholar 

  27. Baert FJ, D'Haens GR, Peeters M, Hiele MI, Schaible TF, Shealy D, Geboes K, Rutgeerts PJ (1999) Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterol 116 (1):22-28

    Article  CAS  Google Scholar 

  28. Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G, Geboes K, Ceuppens JL, Rutgeerts P (2002) Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease. Am J Gastroenterol 97 (8):2000-2004. https://doi.org/10.1111/j.1572-0241.2002.05914.x

    Article  CAS  PubMed  Google Scholar 

  29. Zolotarevsky Y, Hecht G, Koutsouris A, Gonzalez DE, Quan C, Tom J, Mrsny RJ, Turner JR (2002) A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease. Gastroenterol 123 (1):163-172. https://doi.org/10.1053/gast.2002.34235

    Article  CAS  Google Scholar 

  30. Wang F, Graham WV, Wang Y, Witkowski ED, Schwarz BT, Turner JR (2005) Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am J Pathol 166 (2):409-419. https://doi.org/10.1016/s0002-9440(10)62264-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pongkorpsakol P, Turner JR, Zuo L (2020) Culture of Intestinal Epithelial Cell Monolayers and Their Use in Multiplex Macromolecular Permeability Assays for In Vitro Analysis of Tight Junction Size Selectivity. Curr Protoc Immunol 131 (1):e112. https://doi.org/10.1002/cpim.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A (2003) Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 171 (11):6164-6172

    Article  CAS  Google Scholar 

  33. Clayburgh DR, Barrett TA, Tang Y, Meddings JB, Van Eldik LJ, Watterson DM, Clarke LL, Mrsny RJ, Turner JR (2005) Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest 115 (10):2702-2715. https://doi.org/10.1172/JCI24970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Blair SA, Kane SV, Clayburgh DR, Turner JR (2006) Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest 86 (2):191-201. https://doi.org/10.1038/labinvest.3700373

    Article  CAS  PubMed  Google Scholar 

  35. Holmes JL, Van Itallie CM, Rasmussen JE, Anderson JM (2006) Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns. Gene Expr Patterns 6 (6):581-588. https://doi.org/10.1016/j.modgep.2005.12.001

    Article  CAS  PubMed  Google Scholar 

  36. Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Burgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterol 129 (2):550-564. https://doi.org/10.1016/j.gastro.2005.05.002

    Article  CAS  Google Scholar 

  37. Prasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE (2005) Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab Invest 85 (9):1139-1162. https://doi.org/10.1038/labinvest.3700316

    Article  CAS  PubMed  Google Scholar 

  38. 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 (1):61-72. https://doi.org/10.1136/gut.2006.094375

    Article  CAS  PubMed  Google Scholar 

  39. Weber CR, Raleigh DR, Su L, Shen L, Sullivan EA, Wang Y, Turner JR (2010) Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity. J Biol Chem 285 (16):12037-12046. https://doi.org/10.1074/jbc.M109.064808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Raju P, Shashikanth N, Tsai PY, Pongkorpsakol P, Chanez-Paredes S, Steinhagen PR, Kuo WT, Singh G, Tsukita S, Turner JR (2020) Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice. J Clin Invest 130 (10):5197-5208. https://doi.org/10.1172/JCI138697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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 (Pt 3):298-305. https://doi.org/10.1242/jcs.021485

    Article  CAS  PubMed  Google Scholar 

  42. Van Itallie CM, Fanning AS, Bridges A, Anderson JM (2009) ZO-1 stabilizes the tight junction solute barrier through coupling to the perijunctional cytoskeleton. Mol Biol Cell 20 (17):3930-3940. https://doi.org/10.1091/mbc.E09-04-0320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Buschmann MM, Shen L, Rajapakse H, Raleigh DR, Wang Y, Wang Y, Lingaraju A, Zha J, Abbott E, McAuley EM, Breskin LA, Wu L, Anderson K, Turner JR, Weber CR (2013) Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux. Mol Biol Cell 24 (19):3056-3068. https://doi.org/10.1091/mbc.E12-09-0688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9 (11):799-809. https://doi.org/10.1038/nri2653

    Article  CAS  PubMed  Google Scholar 

  45. Anderson JM, Van Itallie CM (2009) Physiology and function of the tight junction. Cold Spring Harb Perspect Biol 1 (2):a002584. https://doi.org/10.1101/cshperspect.a002584

    Article  PubMed  PubMed Central  Google Scholar 

  46. Weber CR, Liang GH, Wang Y, Das S, Shen L, Yu AS, Nelson DJ, Turner JR (2015) Claudin-2-dependent paracellular channels are dynamically gated. eLife 4:e09906. https://doi.org/10.7554/eLife.09906

    Article  PubMed  PubMed Central  Google Scholar 

  47. Krug SM, Amasheh S, Richter JF, Milatz S, Gunzel D, Westphal JK, Huber O, Schulzke JD, Fromm M (2009) Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Mol Biol Cell 20 (16):3713-3724. https://doi.org/10.1091/mbc.E09-01-0080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pappenheimer JR (1993) On the coupling of membrane digestion with intestinal absorption of sugars and amino acids. Am J Physiol 265 (3 Pt 1):G409-417. https://doi.org/10.1152/ajpgi.1993.265.3.G409

    Article  CAS  PubMed  Google Scholar 

  49. Tamura A, Hayashi H, Imasato M, Yamazaki Y, Hagiwara A, Wada M, Noda T, Watanabe M, Suzuki Y, Tsukita S (2011) Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine. Gastroenterol 140 (3):913-923. https://doi.org/10.1053/j.gastro.2010.08.006

    Article  CAS  Google Scholar 

  50. Ong M, Yeruva S, Sailer A, Nilsen SP, Turner JR (2020) Differential regulation of claudin-2 and claudin-15 expression in children and adults with malabsorptive disease. Lab Invest 100 (3):483-490. https://doi.org/10.1038/s41374-019-0324-8

    Article  CAS  PubMed  Google Scholar 

  51. 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 (1):C142-147. https://doi.org/10.1152/ajpcell.00038.2002

    Article  CAS  PubMed  Google Scholar 

  52. Rosenthal R, Gunzel D, Piontek J, Krug SM, Ayala-Torres C, Hempel C, Theune D, Fromm M (2020) Claudin-15 forms a water channel through the tight junction with distinct function compared to claudin-2. Acta Physiol (Oxf) 228 (1):e13334. https://doi.org/10.1111/apha.13334

    Article  CAS  Google Scholar 

  53. Angelow S, Yu AS (2009) Structure-function studies of claudin extracellular domains by cysteine-scanning mutagenesis. J Biol Chem 284 (42):29205-29217. https://doi.org/10.1074/jbc.M109.043752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 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 (1):111-127. https://doi.org/10.1085/jgp.200810154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rosenthal R, Gunzel D, Krug SM, Schulzke JD, Fromm M, Yu AS (2017) Claudin-2-mediated cation and water transport share a common pore. Acta Physiol (Oxf) 219 (2):521-536. https://doi.org/10.1111/apha.12742

    Article  CAS  Google Scholar 

  56. Wada M, Tamura A, Takahashi N, Tsukita S (2013) Loss of claudins 2 and 15 from mice causes defects in paracellular Na+ flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterol 144 (2):369-380. https://doi.org/10.1053/j.gastro.2012.10.035

    Article  CAS  Google Scholar 

  57. Kinugasa T, Sakaguchi T, Gu X, Reinecker HC (2000) Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterol 118 (6):1001-1011

    Article  CAS  Google Scholar 

  58. Nishiyama R, Sakaguchi T, Kinugasa T, Gu X, MacDermott RP, Podolsky DK, Reinecker HC (2001) Interleukin-2 receptor beta subunit-dependent and -independent regulation of intestinal epithelial tight junctions. J Biol Chem 276 (38):35571-35580. https://doi.org/10.1074/jbc.M106013200. M106013200 [pii]

    Article  CAS  PubMed  Google Scholar 

  59. Suzuki T, Yoshinaga N, Tanabe S (2011) Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem 286 (36):31263-31271. https://doi.org/10.1074/jbc.M111.238147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Tsai PY, Zhang B, He WQ, Zha JM, Odenwald MA, Singh G, Tamura A, Shen L, Sailer A, Yeruva S, Kuo WT, Fu YX, Tsukita S, Turner JR (2017) IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance. Cell Host Microbe 21 (6):671-681 e674. https://doi.org/10.1016/j.chom.2017.05.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tamura A, Kitano Y, Hata M, Katsuno T, Moriwaki K, Sasaki H, Hayashi H, Suzuki Y, Noda T, Furuse M, Tsukita S, Tsukita S (2008) Megaintestine in claudin-15-deficient mice. Gastroenterol 134 (2):523-534. https://doi.org/10.1053/j.gastro.2007.11.040

    Article  CAS  Google Scholar 

  62. Chanez-Paredes SD, Abtahi S, Kuo W-T, Turner JR (2021) Differentiating Between Tight Junction-Dependent and Tight Junction-Independent Intestinal Barrier Loss In Vivo. In: Methods in Molecular Biology. Springer US. https://doi.org/10.1007/7651_2021_389

  63. Oami T, Coopersmith CM (2021) Measurement of Intestinal Permeability During Sepsis. Methods Mol Biol 2321:169-175. https://doi.org/10.1007/978-1-0716-1488-4_15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ahmad R, Chaturvedi R, Olivares-Villagomez D, Habib T, Asim M, Shivesh P, Polk DB, Wilson KT, Washington MK, Van Kaer L, Dhawan P, Singh AB (2014) Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis. Mucosal Immunol 7 (6):1340-1353. https://doi.org/10.1038/mi.2014.21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Powrie F, Correa-Oliveira R, Mauze S, Coffman RL (1994) Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med 179 (2):589-600. https://doi.org/10.1084/jem.179.2.589

    Article  CAS  PubMed  Google Scholar 

  66. Ando-Akatsuka Y, Saitou M, Hirase T, Kishi M, Sakakibara A, Itoh M, Yonemura S, Furuse M, Tsukita S (1996) Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues. J Cell Biol 133 (1):43-47. https://doi.org/10.1083/jcb.133.1.43

    Article  CAS  PubMed  Google Scholar 

  67. Li Y, Fanning AS, Anderson JM, Lavie A (2005) Structure of the conserved cytoplasmic C-terminal domain of occludin: identification of the ZO-1 binding surface. J Mol Biol 352 (1):151-164. https://doi.org/10.1016/j.jmb.2005.07.017

    Article  CAS  PubMed  Google Scholar 

  68. Cordenonsi M, Mazzon E, De Rigo L, Baraldo S, Meggio F, Citi S (1997) Occludin dephosphorylation in early development of Xenopus laevis. J Cell Sci 110 (Pt 24):3131-3139

    Article  CAS  Google Scholar 

  69. Cordenonsi M, Turco F, D'Atri F, Hammar E, Martinucci G, Meggio F, Citi S (1999) Xenopus laevis occludin. Identification of in vitro phosphorylation sites by protein kinase CK2 and association with cingulin. Eur J Biochem 264 (2):374-384. https://doi.org/10.1046/j.1432-1327.1999.00616.x

    Article  CAS  PubMed  Google Scholar 

  70. Smales C, Ellis M, Baumber R, Hussain N, Desmond H, Staddon JM (2003) Occludin phosphorylation: identification of an occludin kinase in brain and cell extracts as CK2. FEBS Lett 545 (2-3):161-166.

    Article  CAS  Google Scholar 

  71. Raleigh DR, Boe DM, Yu D, Weber CR, Marchiando AM, Bradford EM, Wang Y, Wu L, Schneeberger EE, Shen L, Turner JR (2011) Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function. J Cell Biol 193 (3):565-582. https://doi.org/10.1083/jcb.201010065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S (1999) Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol 147 (6):1351-1363. https://doi.org/10.1083/jcb.147.6.1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (1998) The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273 (45):29745-29753

    Article  CAS  Google Scholar 

  74. Yu AS (2011) Electrophysiological characterization of claudin ion permeability using stably transfected epithelial cell lines. Methods Mol Biol 762:27-41. https://doi.org/10.1007/978-1-61779-185-7_3

    Article  CAS  PubMed  Google Scholar 

  75. Shashikanth N, Rizzo HE, Pongkorpsakol P, Heneghan JF, Turner JR (2021) Electrophysiologic Analysis of Tight Junction Size and Charge Selectivity. Curr Protoc 1 (6):e143. https://doi.org/10.1002/cpz1.143

    Article  CAS  PubMed  Google Scholar 

  76. Marchiando AM, Shen L, Graham WV, Weber CR, Schwarz BT, Austin JR, 2nd, Raleigh DR, Guan Y, Watson AJ, Montrose MH, Turner JR (2010) Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. J Cell Biol 189 (1):111-126. https://doi.org/10.1083/jcb.200902153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pearson AD, Eastham EJ, Laker MF, Craft AW, Nelson R (1982) Intestinal permeability in children with Crohn's disease and coeliac disease. Br Med J (Clin Res Ed) 285 (6334):20-21

    Article  CAS  Google Scholar 

  78. Olaison G, Leandersson P, Sjodahl R, Tagesson C (1988) Intestinal permeability to polyethyleneglycol 600 in Crohn's disease. Peroperative determination in a defined segment of the small intestine. Gut 29 (2):196-199. https://doi.org/10.1136/gut.29.2.196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11 (12):4131-4142. https://doi.org/10.1091/mbc.11.12.4131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kitajiri S, Katsuno T, Sasaki H, Ito J, Furuse M, Tsukita S (2014) Deafness in occludin-deficient mice with dislocation of tricellulin and progressive apoptosis of the hair cells. Biology open 3 (8):759-766. https://doi.org/10.1242/bio.20147799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kuo WT, Shen L, Zuo L, Shashikanth N, Ong M, Wu L, Zha J, Edelblum KL, Wang Y, Wang Y, Nilsen SP, Turner JR (2019) Inflammation-induced Occludin Downregulation Limits Epithelial Apoptosis by Suppressing Caspase-3 Expression. Gastroenterol 157 (5):1323-1337. https://doi.org/10.1053/j.gastro.2019.07.058

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank previous and current members of the Laboratory of Mucosal Barrier Pathobiology for their intellectual contributions to the development of studies described herein and for allowing the reuse of their published data. We are also indebted to Tiffany S. Davanzo (Slaybaugh Studios) and Heather Marlatt (Nationwide Histology) for their contributions to the figures. Finally, although we have attempted to cite previous work correctly and completely, we are certain to have omitted some studies, either unintentionally or due to space limitations, and offer our apologies to those we have failed to acknowledge.

Funding: This work was supported by the National Institutes of Health grants R01DK061931 (JRT), R01DK068271 (JRT), and P30DK034854 (The Harvard Digestive Disease Center).

Author information

Author notes

  1. Wei-Ting Kuo

    Present address: Graduate Institute of Oral Biology, National Taiwan University, Taipei, Taiwan

Authors and Affiliations

  1. Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Yan Y. Sweat, Shabnam Abtahi, Sandra D. Chanez-Paredes, Preeti Raju, Li Zuo, Nitesh Shashikanth, Wei-Ting Kuo & Jerrold R. Turner

  2. Anhui Medical University, Hefei, Anhui, China

    Li Zuo

Authors
  1. Yan Y. Sweat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shabnam Abtahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra D. Chanez-Paredes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Preeti Raju
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nitesh Shashikanth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei-Ting Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jerrold R. Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jerrold R. Turner .

Editor information

Editors and Affiliations

  1. Department of Physiology, Biophysics, and Neuroscience, Center for Research and Advance Studies (Cinvestav), Mexico City, Mexico

    Lorenza González-Mariscal

Ethics declarations

JRT is a founder and shareholder of Thelium Therapeutics and has served as a consultant for Entrinsic, Immunic, and Kallyope.

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sweat, Y.Y. et al. (2022). Modulation of Intestinal Disorders by Claudin-2 and Occludin Via Canonical and Noncanonical Mechanisms. In: González-Mariscal, L. (eds) Tight Junctions. Springer, Cham. https://doi.org/10.1007/978-3-030-97204-2_5

Download citation

Publish with us

Policies and ethics

Search

Navigation