| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany; and
Institute of Pathology, University of Tübingen, Tübingen, Germany
3 Correspondence: Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125 Berlin, Germany. E-mail: gkrause{at}fmp-berlin.de
Claudins are the critical transmembrane proteins in tight junctions. Claudin-5, for instance, prevents paracellular permeation of small molecules. However, the molecular interaction mechanism is unknown. Hence, the claudin-claudin interaction and tight junction strand formation were investigated using systematic single mutations. Claudin-5 mutants transfected into tight junction-free cells demonstrated that the extracellular loop 2 is involved in strand formation via trans-interaction, but not via polymerization, along the plasma membrane of one cell. Three phenotypes were obtained: the tight junction type (wild-type-like trans- and cis-interaction; the disjunction type (blocked trans-interaction); the intracellular type (disturbed folding). Combining site-directed mutagenesis, live-cell imaging-, electron microscopy-, and molecular modeling data led to an antiparallel homodimer homology model of the loop. These data for the first time explain how two claudins hold onto each other and constrict the paracellular space. The intermolecular interface includes aromatic (F147, Y148, Y158) and hydrophilic (Q156, E159) residues. The aromatic residues form a strong binding core between two loops from opposing cells. Since nearly all these residues are conserved in most claudins, our findings are of general relevance for all classical claudins. On the basis of the data we have established a novel molecular concept for tight junction formation.—Piontek, J., Winkler, L., Wolburg, H., Müller, S. L., Zuleger, N., Piehl, C., Wiesner, B., Krause, G., Blasig, I. E. Formation of tight junction: determinants of homophilic interaction between classic claudins.
Key Words: transmembrane protein • protein-protein interaction • cell-cell contacts • freeze-fracturing • FRET
This article has been cited by other articles:
|
|
 |
|
  M. Burek, P. A. Arias-Loza, N. Roewer, and C. Y. Forster Claudin-5 as a Novel Estrogen Target in Vascular Endothelium Arterioscler Thromb Vasc Biol, February 1, 2010; 30(2): 298 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, J. Piontek, H. Wolburg, C. Piehl, M. Liss, C. Otten, A. Christ, T. E. Willnow, I. E. Blasig, and S. Abdelilah-Seyfried Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion PNAS, January 26, 2010; 107(4): 1425 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Robertson, J. G. Smedley III, and B. A. McClane Identification of a Claudin-4 Residue Important for Mediating the Host Cell Binding and Action of Clostridium perfringens Enterotoxin Infect. Immun., January 1, 2010; 78(1): 505 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kimura, H. Abe, S. Kamitani, H. Toshima, A. Fukui, M. Miyake, Y. Kamata, Y. Sugita-Konishi, S. Yamamoto, and Y. Horiguchi Clostridium perfringens Enterotoxin Interacts with Claudins via Electrostatic Attraction J. Biol. Chem., January 1, 2010; 285(1): 401 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tatum, Y. Zhang, K. Salleng, Z. Lu, J.-J. Lin, Q. Lu, B. G. Jeansonne, L. Ding, and Y.-H. Chen Renal salt wasting and chronic dehydration in claudin-7-deficient mice Am J Physiol Renal Physiol, January 1, 2010; 298(1): F24 - F34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M.K. Morrow, G. Tyagi, L. Simon, K. Carnes, K. M. Murphy, P. S. Cooke, M.-C. C. Hofmann, and R. A. Hess Claudin 5 Expression in Mouse Seminiferous Epithelium Is Dependent upon the Transcription Factor Ets Variant 5 and Contributes to Blood-Testis Barrier Function Biol Reprod, November 1, 2009; 81(5): 871 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Campbell, A. T. H. Nguyen, A.-S. Kiang, L. C. S. Tam, O. L. Gobbo, C. Kerskens, S. N. Dhubhghaill, M. M. Humphries, G.-J. Farrar, P. F. Kenna, et al. An experimental platform for systemic drug delivery to the retina PNAS, October 20, 2009; 106(42): 17817 - 17822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Angelow and A. S. L. Yu Structure-Function Studies of Claudin Extracellular Domains by Cysteine-scanning Mutagenesis J. Biol. Chem., October 16, 2009; 284(42): 29205 - 29217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hou, A. Renigunta, A. S. Gomes, M. Hou, D. L. Paul, S. Waldegger, and D. A. Goodenough Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium PNAS, September 8, 2009; 106(36): 15350 - 15355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Krug, S. Amasheh, J. F. Richter, S. Milatz, D. Gunzel, J. K. Westphal, O. Huber, J. D. Schulzke, and M. Fromm Tricellulin Forms a Barrier to Macromolecules in Tricellular Tight Junctions without Affecting Ion Permeability Mol. Biol. Cell, August 15, 2009; 20(16): 3713 - 3724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Winkler, C. Gehring, A. Wenzel, S. L. Muller, C. Piehl, G. Krause, I. E. Blasig, and J. Piontek Molecular Determinants of the Interaction between Clostridium perfringens Enterotoxin Fragments and Claudin-3 J. Biol. Chem., July 10, 2009; 284(28): 18863 - 18872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Mee, H. J. Harris, M. J. Farquhar, G. Wilson, G. Reynolds, C. Davis, S. C. D. van IJzendoorn, P. Balfe, and J. A. McKeating Polarization Restricts Hepatitis C Virus Entry into HepG2 Hepatoma Cells J. Virol., June 15, 2009; 83(12): 6211 - 6221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yoshida, Y. Ban, and S. Kinoshita Tight Junction Transmembrane Protein Claudin Subtype Expression and Distribution in Human Corneal and Conjunctival Epithelium Invest. Ophthalmol. Vis. Sci., May 1, 2009; 50(5): 2103 - 2108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wolburg, S. Noell, K. Wolburg-Buchholz, A. Mack, and P. Fallier-Becker Agrin, Aquaporin-4, and Astrocyte Polarity as an Important Feature of the Blood-Brain Barrier Neuroscientist, April 1, 2009; 15(2): 180 - 193. [Abstract] [PDF]
|
|
|
|
|
|
S. Liu, W. Yang, L. Shen, J. R. Turner, C. B. Coyne, and T. Wang Tight Junction Proteins Claudin-1 and Occludin Control Hepatitis C Virus Entry and Are Downregulated during Infection To Prevent Superinfection J. Virol., February 15, 2009; 83(4): 2011 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Timpe and J A McKeating Hepatitis C virus entry: possible targets for therapy Gut, December 1, 2008; 57(12): 1728 - 1737. [Full Text] [PDF]
|
|
|
|
|
|
D. B. N. Lee, N. Jamgotchian, S. G. Allen, M. B. Abeles, and H. J. Ward A lipid-protein hybrid model for tight junction Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1601 - F1612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Angelow, R. Ahlstrom, and A. S. L. Yu Biology of claudins Am J Physiol Renal Physiol, October 1, 2008; 295(4): F867 - F876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. McColl, N. J. Rothwell, and S. M. Allan Systemic Inflammation Alters the Kinetics of Cerebrovascular Tight Junction Disruption after Experimental Stroke in Mice J. Neurosci., September 17, 2008; 28(38): 9451 - 9462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Harris, M. J. Farquhar, C. J. Mee, C. Davis, G. M. Reynolds, A. Jennings, K. Hu, F. Yuan, H. Deng, S. G. Hubscher, et al. CD81 and Claudin 1 Coreceptor Association: Role in Hepatitis C Virus Entry J. Virol., May 15, 2008; 82(10): 5007 - 5020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Mrsny, G. T. Brown, K. Gerner-Smidt, A. G. Buret, J. B. Meddings, C. Quan, M. Koval, and A. Nusrat A Key Claudin Extracellular Loop Domain is Critical for Epithelial Barrier Integrity Am. J. Pathol., April 1, 2008; 172(4): 905 - 915. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
