Tight junction

Last updated
Tight junction
Cellular tight junction en.svg
Diagram of tight junction
Details
Identifiers
Latin junctio occludens
MeSH D019108
TH H1.00.01.1.02007
FMA 67397
Anatomical terminology

Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens), are multiprotein junctional complexes between epithelial cells, [1] sealing and preventing leakage of solutes and water. They also play a critical role maintaining the structure and permeability of endothelial cells. [1] Tight junctions may also serve as leaky pathways by forming selective channels for small cations, anions, or water. The corresponding junctions that occur in invertebrates are septate junctions.

Contents

Structure

Tight junctions are composed of a branching network of sealing strands, each strand acting independently from the others. Therefore, the efficiency of the junction in preventing ion passage increases exponentially with the number of strands. Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly. There are at least 40 different proteins composing the tight junctions. [2] These proteins consist of both transmembrane and cytoplasmic proteins. The three major transmembrane proteins are occludin, claudins, and junction adhesion molecule (JAM) proteins. These associate with different peripheral membrane proteins such as ZO-1 located on the intracellular side of plasma membrane, which anchor the strands to the actin component of the cytoskeleton. [3] In this way, tight junctions join together the cytoskeletons of adjacent cells. Investigation using freeze-fracture methods in electron microscopy is ideal for revealing the lateral extent of tight junctions in cell membranes and has been useful in showing how tight junctions are formed. [4]

Depiction of the transmembrane proteins that make up tight junctions: occludin, claudins, and JAM proteins. Tight Junction Transmembrane Proteins.jpg
Depiction of the transmembrane proteins that make up tight junctions: occludin, claudins, and JAM proteins.

Functions

TEM of rat kidney tissue shows a protein dense tight junction (three dark lines) at ~55,000x magnification. Tight junction blowup.jpg
TEM of rat kidney tissue shows a protein dense tight junction (three dark lines) at ~55,000x magnification.

Tight junctions provide endothelial and epithelial cells with barrier function, which can be further subdivided into protective barriers and functional barriers serving purposes such as material transport and maintenance of osmotic balance. [19]

Tight junctions prevent the passage of molecules and ions through the intercellular space of adjacent cells, so materials must actually enter the cells (by diffusion or active transport) in order to pass through the tissue. The constrained intracellular pathway exacted by the tight junction barrier system allows precise control over which substances can pass through a particular tissue (e.g. the blood–brain barrier). At the present time, it is still unclear whether the control is active or passive and how these pathways are formed. In one study for paracellular transport across the tight junction in kidney proximal tubule, a dual pathway model was proposed, consisting of large slit breaks formed by infrequent discontinuities in the tight junction complex and numerous small circular pores. [20]

Tight junctions also help maintain the apicobasal polarity of cells by preventing the lateral diffusion of integral membrane proteins between the apical and lateral/basal surfaces, allowing the specialized functions of each surface (for example receptor-mediated endocytosis at the apical surface and exocytosis at the basolateral surface) to be preserved. This allows polarized transcellular transport and specialized functions of apical and basolateral membranes.

Occludin interacting with GEF-H1/Lfc, which then activates RHOA, a regulator of cell differentiation and motility. Occludin signaling.jpg
Occludin interacting with GEF-H1/Lfc, which then activates RHOA, a regulator of cell differentiation and motility.

Although classically known for their role in the prevention of paracellular transport, tight junction proteins also play crucial roles as signaling molecules. Occludin is able to interact with signaling pathways controlling cellular differentiation, and has been shown to travel to the nucleus of cells in which the tight junction has been disrupted. There it interacts with transcription factors to initiate apoptosis. [7] [8] ZO-1 is able to regulate cellular migration and proliferation, inhibiting proliferation transcription factors when the cellular tight junction has been established. [8] Claudins, and angulins, like ZO-1, have been shown to interact with several important transcription factors influencing cellular migration and proliferation. These functions of tight junction proteins make the tight junction an important area of study in cancer research. [21]

Classification

Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement: [22]

See also

References

  1. 1 2 Bhat, Ajaz A.; Uppada, Srijayaprakash; Achkar, Iman W.; Hashem, Sheema; Yadav, Santosh K.; Shanmugakonar, Muralitharan; Al-Naemi, Hamda A.; Haris, Mohammad; Uddin, Shahab (2019). "Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk". Frontiers in Physiology. 9: 1942. doi: 10.3389/fphys.2018.01942 . ISSN   1664-042X. PMC   6351700 . PMID   30728783.
  2. Itallie, Christina M. Van; Anderson, James M. (2009-08-01). "Physiology and Function of the Tight Junction". Cold Spring Harbor Perspectives in Biology. 1 (2): a002584. doi:10.1101/cshperspect.a002584. ISSN   1943-0264. PMC   2742087 . PMID   20066090.
  3. Anderson, JM; Van Itallie, CM (August 2009). "Physiology and function of the tight junction". Cold Spring Harb Perspect Biol. 1 (2): a002584. doi:10.1101/cshperspect.a002584. PMC   2742087 . PMID   20066090.
  4. Chalcroft, J. P.; Bullivant, S (1970). "An interpretation of liver cell membrane and junction structure based on observation of freeze-fracture replicas of both sides of the fracture". The Journal of Cell Biology. 47 (1): 49–60. doi:10.1083/jcb.47.1.49. PMC   2108397 . PMID   4935338.
  5. Wolburg, Hartwig; Lippoldt, Andrea; Ebnet, Klaus (2006), "Tight Junctions and the Blood-Brain Barrier", Tight Junctions, Springer US, pp. 175–195, doi:10.1007/0-387-36673-3_13, ISBN   9780387332017
  6. Liu, Wei-Ye; Wang, Zhi-Bin; Zhang, Li-Chao; Wei, Xin; Li, Ling (2012-06-12). "Tight Junction in Blood-Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances". CNS Neuroscience & Therapeutics. 18 (8): 609–615. doi:10.1111/j.1755-5949.2012.00340.x. ISSN   1755-5930. PMC   6493516 . PMID   22686334.
  7. 1 2 Beeman, N; Webb, P G; Baumgartner, H K (2012-02-23). "Occludin is required for apoptosis when claudin–claudin interactions are disrupted". Cell Death & Disease. 3 (2): e273. doi:10.1038/cddis.2012.14. ISSN   2041-4889. PMC   3288343 . PMID   22361748.
  8. 1 2 3 4 Matter, Karl; Aijaz, Saima; Tsapara, Anna; Balda, Maria S (2005-10-01). "Mammalian tight junctions in the regulation of epithelial differentiation and proliferation". Current Opinion in Cell Biology. Cell-to-cell contact and extracellular matrix. 17 (5): 453–458. doi:10.1016/j.ceb.2005.08.003. ISSN   0955-0674. PMID   16098725.
  9. Schneeberger, Eveline E.; Lynch, Robert D. (June 2004). "The tight junction: a multifunctional complex" (PDF). American Journal of Physiology. Cell Physiology. 286 (6): C1213 –C1228. doi:10.1152/ajpcell.00558.2003. ISSN   0363-6143. PMID   15151915. S2CID   1725292. Archived from the original (PDF) on 2019-02-22.
  10. Mitic, Laura L.; Van Itallie, Christina M.; Anderson, James M. (August 2000). "Molecular Physiology and Pathophysiology of Tight Junctions I. Tight junction structure and function: lessons from mutant animals and proteins" (PDF). American Journal of Physiology. Gastrointestinal and Liver Physiology. 279 (2): G250 –G254. doi:10.1152/ajpgi.2000.279.2.g250. ISSN   0193-1857. PMID   10915631. S2CID   32634345. Archived from the original (PDF) on 2019-03-09.
  11. Ebnet, Klaus (2017-10-01). "Junctional Adhesion Molecules (JAMs): Cell Adhesion Receptors With Pleiotropic Functions in Cell Physiology and Development". Physiological Reviews. 97 (4): 1529–1554. doi:10.1152/physrev.00004.2017. ISSN   0031-9333. PMID   28931565. S2CID   10846721.
  12. Luissint, Anny-Claude; Artus, Cédric; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier (2012-11-09). "Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation". Fluids and Barriers of the CNS. 9 (1): 23. doi: 10.1186/2045-8118-9-23 . ISSN   2045-8118. PMC   3542074 . PMID   23140302.
  13. Hartmann, Christian; Schwietzer, Ysabel Alessa; Otani, Tetsuhisa; Furuse, Mikio; Ebnet, Klaus (2020-09-01). "Physiological functions of junctional adhesion molecules (JAMs) in tight junctions". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1862 (9): 183299. doi:10.1016/j.bbamem.2020.183299. ISSN   0005-2736. PMID   32247783.
  14. Luissint, Anny-Claude; Artus, Cédric; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier (2012-11-09). "Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation". Fluids and Barriers of the CNS. 9 (1): 23. doi: 10.1186/2045-8118-9-23 . ISSN   2045-8118. PMC   3542074 . PMID   23140302.
  15. Ley, Klaus; Laudanna, Carlo; Cybulsky, Myron I.; Nourshargh, Sussan (September 2007). "Getting to the site of inflammation: the leukocyte adhesion cascade updated". Nature Reviews Immunology. 7 (9): 678–689. doi:10.1038/nri2156. ISSN   1474-1741. PMID   17717539.
  16. Masuda, Sayuri; Oda, Yukako; Sasaki, Hiroyuki; Ikenouchi, Junichi; Higashi, Tomohito; Akashi, Masaya; Nishi, Eiichiro; Furuse, Mikio (2011-02-15). "LSR definescell corners for tricellular tight junction formation in epithelial cells". Journal of Cell Science. 124 (Part 4): 548–555. doi: 10.1242/jcs.072058 . PMID   21245199.
  17. Higashi, Tomohito; Miller, Ann (2017-07-15). "Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells". Molecular Biology of the Cell. 28 (15): 2023–2034. doi:10.1091/mbc.E16-10-0697. ISSN   1939-4586. PMC   5509417 . PMID   28705832.
  18. "UniProt". www.uniprot.org. Retrieved 2024-12-06.
  19. Department, Biology. "Tight Junctions (and other cellular connections)". Davidson College. Retrieved 2015-01-12.
  20. Guo, P; Weinstein, AM; Weinbaum, S (Aug 2003). "A dual-pathway ultrastructural model for the tight junction of rat proximal tubule epithelium" (PDF). American Journal of Physiology. Renal Physiology. 285 (2): F241–57. doi:10.1152/ajprenal.00331.2002. PMID   12670832. S2CID   22824832. Archived from the original (PDF) on 2019-02-22.
  21. Sugimoto, Kotaro; Chiba, Hideki (2021-07-03). "The claudin–transcription factor signaling pathway". Tissue Barriers. 9 (3). doi:10.1080/21688370.2021.1908109. PMC   8489944 . PMID   33906582.
  22. Department, Biology. "Tight Junctions and other cellular connections". Davidson College. Retrieved 2013-09-20.