![Electron micographs of retinal pigment epithelial and endothelial tight junctions… Electron micographs of retinal pigment epithelial and endothelial tight junctions…](https://www.ucl.ac.uk/ioo/sites/ioo/files/styles/small_image/public/migrated-images/EMRPEendojunctions.jpg?itok=yItUUi-B)
Morphology and Structure
- Tight junctions are intercellular adhesion complexes of epithelial and endothelial cells that form close membrane-membrane contacts
- Tight junctions are composed of an intricate protein network composed of transmembrane proteins and cytosolic proteins
![Scheme of the molecular composition of tight junctions… Scheme of the molecular composition of tight junctions…](https://www.ucl.ac.uk/ioo/sites/ioo/files/styles/medium_image/public/migrated-images/Slide3_0.jpg?itok=nf71ljgl)
Functions
- Tight junctions form diffusion barriers between neighboring cells that regulate permeability across epithelia and endothelia
- Tight junctions support maintenance of cell surface polarity by forming an intramembrane diffusion barrier that restricts diffusion of lipids in the exoplasmic leaflet of the plasma membrane
![Diffusion of fluorescent lipids across tight junctions in cells expressing a mutant tight junction protein but not in wild type cells… Diffusion of fluorescent lipids across tight junctions in cells expressing a mutant tight junction protein but not in wild type cells…](https://www.ucl.ac.uk/ioo/sites/ioo/files/styles/medium_image/public/migrated-images/Diffusionbarrier.jpg?itok=rVU36AFS)
- Tight junctions regulate signalling pathways that control epithelial proliferation, differentiation and polarization
- Tight junctions form bidirectional signalling hubs that receive signals from the cells that regulate junctional functions and that transmit signals to the cells to guide cell behaviour and differentiation
![Signalling to and from tight junctions… Signalling to and from tight junctions…](https://www.ucl.ac.uk/ioo/sites/ioo/files/styles/medium_image/public/migrated-images/Slide1_0.jpg?itok=QV8gQbyM)
Recent and key publications
Reviews
1. Zihni, C., et al., Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol, 2016. 10.1038/nrm.2016.80;
http://www.ncbi.nlm.nih.gov/pubmed/27353478
2. Balda, M.S. and K. Matter, Tight junctions as regulators of tissue remodelling. Curr Opin Cell Biol, 2016. 42: p. 94-101. 10.1016/j.ceb.2016.05.006;
http://www.ncbi.nlm.nih.gov/pubmed/27236618
3. Zihni, C., M.S. Balda, and K. Matter, Signalling at tight junctions during epithelial differentiation and microbial pathogenesis. J Cell Sci, 2014. 127(Pt 16): p. 3401-13. 10.1242/jcs.145029;
http://www.ncbi.nlm.nih.gov/pubmed/25125573
4. Matter, K. and M.S. Balda, SnapShot: Epithelial tight junctions. Cell, 2014. 157(4): p. 992-992 e1. 10.1016/j.cell.2014.04.027;
http://www.ncbi.nlm.nih.gov/pubmed/24813618
5. Balda, M.S. and K. Matter, Tight junctions in health and disease. Semin Cell Dev Biol, 2014. 36: p. 147-8. 10.1016/j.semcdb.2014.11.001;
http://www.ncbi.nlm.nih.gov/pubmed/25454390
6. Terry, S., et al., Rho signaling and tight junction functions. Physiology (Bethesda), 2010. 25(1): p. 16-26. 10.1152/physiol.00034.2009;
http://www.ncbi.nlm.nih.gov/pubmed/20134025
7. Steed, E., M.S. Balda, and K. Matter, Dynamics and functions of tight junctions. Trends Cell Biol, 2010. 20(3): p. 142-9. 10.1016/j.tcb.2009.12.002;
http://www.ncbi.nlm.nih.gov/pubmed/20061152
Research papers
1. Zihni, C., et al., Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol, 2016.
10.1038/nrm.2016.80;
http://www.ncbi.nlm.nih.gov/pubmed/27353478
2. Balda, M.S. and K. Matter, Tight junctions as regulators of tissue remodelling. Curr Opin Cell Biol, 2016. 42: p. 94-101.
10.1016/j.ceb.2016.05.006;
http://www.ncbi.nlm.nih.gov/pubmed/27236618
3. Tornavaca, O., et al., ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. J Cell Biol, 2015. 208(6): p. 821-38.
10.1083/jcb.201404140; PMC4362456
http://www.ncbi.nlm.nih.gov/pubmed/25753039
4. Zihni, C., M.S. Balda, and K. Matter, Signalling at tight junctions during epithelial differentiation and microbial pathogenesis. J Cell Sci, 2014. 127(Pt 16): p. 3401-13.
10.1242/jcs.145029;
http://www.ncbi.nlm.nih.gov/pubmed/25125573
5. Steed, E., et al., MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival. J Cell Biol, 2014. 204(5): p. 821-38.
10.1083/jcb.201304115; PMC3941049
http://www.ncbi.nlm.nih.gov/pubmed/24567356
6. Matter, K. and M.S. Balda, SnapShot: Epithelial tight junctions. Cell, 2014. 157(4): p. 992-992 e1.
10.1016/j.cell.2014.04.027;
http://www.ncbi.nlm.nih.gov/pubmed/24813618
7. Balda, M.S. and K. Matter, Tight junctions in health and disease. Semin Cell Dev Biol, 2014. 36: p. 147-8.
10.1016/j.semcdb.2014.11.001;
http://www.ncbi.nlm.nih.gov/pubmed/25454390
8. Nie, M., M.S. Balda, and K. Matter, Stress- and Rho-activated ZO-1-associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival. Proc Natl Acad Sci U S A, 2012. 109(27): p. 10897-902.
10.1073/pnas.1118822109; PMC3390842
http://www.ncbi.nlm.nih.gov/pubmed/22711822
9. Elbediwy, A., et al., Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex. J Cell Biol, 2012. 198(4): p. 677-93.
10.1083/jcb.201202094; PMC3514035
http://www.ncbi.nlm.nih.gov/pubmed/22891260
10. Terry, S.J., et al., Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nat Cell Biol, 2011. 13(2): p. 159-66.
10.1038/ncb2156; PMC3032653
http://www.ncbi.nlm.nih.gov/pubmed/21258369
11. Tsapara, A., et al., The RhoA activator GEF-H1/Lfc is a transforming growth factor-beta target gene and effector that regulates alpha-smooth muscle actin expression and cell migration. Mol Biol Cell, 2010. 21(6): p. 860-70.
10.1091/mbc.E09-07-0567; PMC2836967
http://www.ncbi.nlm.nih.gov/pubmed/20089843
12. Terry, S., et al., Rho signaling and tight junction functions. Physiology (Bethesda), 2010. 25(1): p. 16-26.
10.1152/physiol.00034.2009;
http://www.ncbi.nlm.nih.gov/pubmed/20134025
13. Steed, E., M.S. Balda, and K. Matter, Dynamics and functions of tight junctions. Trends Cell Biol, 2010. 20(3): p. 142-9.
10.1016/j.tcb.2009.12.002;
http://www.ncbi.nlm.nih.gov/pubmed/20061152
14. Lima, W.R., et al., ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells. J Am Soc Nephrol, 2010. 21(3): p. 478-88.
10.1681/ASN.2009070698; PMC2831853
http://www.ncbi.nlm.nih.gov/pubmed/20133480
15. Larre, I., et al., Ouabain modulates epithelial cell tight junction. Proc Natl Acad Sci U S A, 2010. 107(25): p. 11387-92.
10.1073/pnas.1000500107; PMC2895057
http://www.ncbi.nlm.nih.gov/pubmed/20534449
16. Georgiadis, A., et al., The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice. PLoS One, 2010. 5(12): p. e15730.
10.1371/journal.pone.0015730; PMC3012699
http://www.ncbi.nlm.nih.gov/pubmed/21209887
17. Steed, E., et al., Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC Cell Biol, 2009. 10: p. 95.
10.1186/1471-2121-10-95; PMC2805614
http://www.ncbi.nlm.nih.gov/pubmed/20028514
18. Nie, M., et al., The Y-box factor ZONAB/DbpA associates with GEF-H1/Lfc and mediates Rho-stimulated transcription. EMBO Rep, 2009. 10(10): p. 1125-31.
10.1038/embor.2009.182; PMC2738780
http://www.ncbi.nlm.nih.gov/pubmed/19730435
19. Tsapara, A., K. Matter, and M.S. Balda, The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB. Mol Biol Cell, 2006. 17(3): p. 1322-30.
10.1091/mbc.E05-06-0507; PMC1382320
http://www.ncbi.nlm.nih.gov/pubmed/16407410
20. Sourisseau, T., et al., Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Mol Cell Biol, 2006. 26(6): p. 2387-98.
10.1128/MCB.26.6.2387-2398.2006; PMC1430269
http://www.ncbi.nlm.nih.gov/pubmed/16508013
21. Kavanagh, E., et al., Functional interaction between the ZO-1-interacting transcription factor ZONAB/DbpA and the RNA processing factor symplekin. J Cell Sci, 2006. 119(Pt 24): p. 5098-105.
10.1242/jcs.03297;
http://www.ncbi.nlm.nih.gov/pubmed/17158914
22. Frankel, P., et al., RalA interacts with ZONAB in a cell density-dependent manner and regulates its transcriptional activity. EMBO J, 2005. 24(1): p. 54-62.
10.1038/sj.emboj.7600497; PMC544910
http://www.ncbi.nlm.nih.gov/pubmed/15592429
23. Aijaz, S., et al., Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Dev Cell, 2005. 8(5): p. 777-86.
10.1016/j.devcel.2005.03.003;
http://www.ncbi.nlm.nih.gov/pubmed/15866167
24. Benais-Pont, G., et al., Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. J Cell Biol, 2003. 160(5): p. 729-40.
10.1083/jcb.200211047; PMC2173357
http://www.ncbi.nlm.nih.gov/pubmed/12604587
25. Balda, M.S., M.D. Garrett, and K. Matter, The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density. J Cell Biol, 2003. 160(3): p. 423-32.
10.1083/jcb.200210020; PMC2172662
http://www.ncbi.nlm.nih.gov/pubmed/12566432
26. Huber, D., M.S. Balda, and K. Matter, Occludin modulates transepithelial migration of neutrophils. J Biol Chem, 2000. 275(8): p. 5773-8.
http://www.ncbi.nlm.nih.gov/pubmed/10681565
27. Balda, M.S., et al., Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem, 2000. 78(1): p. 85-96.
http://www.ncbi.nlm.nih.gov/pubmed/10797568
28. Balda, M.S. and K. Matter, The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J, 2000. 19(9): p. 2024-33.
10.1093/emboj/19.9.2024; PMC305688
http://www.ncbi.nlm.nih.gov/pubmed/10790369
29. Matter, K. and M.S. Balda, Biogenesis of tight junctions: the C-terminal domain of occludin mediates basolateral targeting. J Cell Sci, 1998. 111 ( Pt 4): p. 511-9.
http://www.ncbi.nlm.nih.gov/pubmed/9443899
30. Balda, M.S., et al., Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J Cell Biol, 1996. 134(4): p. 1031-49.
PMC2120963
http://www.ncbi.nlm.nih.gov/pubmed/8769425
31. Willott, E., et al., The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc Natl Acad Sci U S A, 1993. 90(16): p. 7834-8.
PMC47237
http://www.ncbi.nlm.nih.gov/pubmed/8395056
32. Balda, M.S., et al., Assembly of the tight junction: the role of diacylglycerol. J Cell Biol, 1993. 123(2): p. 293-302.
PMC2119828
http://www.ncbi.nlm.nih.gov/pubmed/8408213
33. Balda, M.S. and J.M. Anderson, Two classes of tight junctions are revealed by ZO-1 isoforms. Am J Physiol, 1993. 264(4 Pt 1): p. C918-24.
http://www.ncbi.nlm.nih.gov/pubmed/7682777
34. Balda, M.S., et al., Assembly and sealing of tight junctions: possible participation of G-proteins, phospholipase C, protein kinase C and calmodulin. J Membr Biol, 1991. 122(3): p. 193-202.