Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epithelial cells.[1] 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.
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] Thus, tight junctions join together the cytoskeletons of adjacent cells.
Depiction of the transmembrane proteins that make up tight junctions: occludin, claudins, and JAM proteins.
Transmembrane proteins:
Occludin was the first integral membrane protein to be identified. It has a molecular weight of ~60kDa. It consists of four transmembrane domains and both the N-terminus and the C-terminus of the protein are intracellular. It forms two extracellular loops and one intracellular loop. These loops help regulate paracellular permeability.[4] Occludin also plays a key role in cellular structure and barrier function.[5]
Claudins were discovered after occludin and are a family of over 27 different members in mammals.[6] They have a molecular weight of ~20kDa. They have a structure similar to that of occludin in that they have four transmembrane domains and similar loop structure. They are understood to be the backbone of tight junctions and play a significant role in the tight junction's ability to seal the paracellular space.[7]
Junctional Adhesion Molecules (JAM) are part of the immunoglobulin superfamily. They have a molecular weight of ~40 to 48 kDa.[8] Their structure differs from that of the other integral membrane proteins in that they only have one transmembrane domain instead of four. It helps to regulate the paracellular pathway function of tight junctions and is also involved in helping to maintain cell polarity.[9]
Angulins were discovered in 2011 by visual screening of proteins which localize at tricellular tight junctions.[10] There are three members of angulins, Angulin-1/LSR, Angulin-2/ILDR1, and Angulin-3/ILDR2. Similar to JAMs, angulins are single-transmembrane proteins. All angulins have one immunoglobulin-like domain in the extracellular region and one PDZ-binding motif at the carboxy-terminus. They are responsible for establishment of tricellular tight junctions and regulate the paracellular barrier function.[11]
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:
Tight junctions prevent the passage of molecules and ions through the space between plasma membranes of adjacent cells, so materials must actually enter the cells (by diffusion or active transport) in order to pass through the tissue. 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.[13] The constrained intracellular pathway exacted by the tight junction barrier system allows precise control over which substances can pass through a particular tissue. (Tight junctions play this role in maintaining 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 is proposed: large slit breaks formed by infrequent discontinuities in the TJ complex and numerous small circular pores.[14]
Tight junctions help to 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 specialised functions of apical and basolateral membranes.
ClassificationEdit
Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement:[15]
Leaky epithelia do not have these tight junctions, or have less complex tight junctions. For instance, the tight junction in the kidney proximal tubule, a very leaky epithelium, has only two to three junctional strands, and these strands exhibit infrequent large slit breaks.
TEM of negatively stained proximal convoluted tubule of Rat kidney tissue at a magnification of ~55,000x and 80 kV with Tight junction. Note that the three dark lines of density correspond to the density of the protein complex, and the light lines in between correspond to the paracellular space.
^ abBhat, 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. PMC6351700. PMID 30728783.
^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. PMC2742087. PMID 20066090.
^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. PMC2742087. PMID 20066090.
^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, ISBN9780387332017
^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. PMC6493516. PMID 22686334.
^Schneeberger, Eveline E.; Lynch, Robert D. (June 2004). (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.
^Mitic, Laura L.; Van Itallie, Christina M.; Anderson, James M. (August 2000). (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.
^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.
^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. PMC3542074. PMID 23140302.
^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. PMC5509417. PMID 28705832.
^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. PMC2108397. PMID 4935338.
^Guo, P; Weinstein, AM; Weinbaum, S (Aug 2003). (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.
^Department, Biology. "Tight Junctions and other cellular connections". Davidson College. Retrieved 2013-09-20.
External linksEdit
Wikimedia Commons has media related to Tight junctions.
Histology image: 20502loa – Histology Learning System at Boston University
October 21, 2023
tight, junction, also, known, occluding, junctions, zonulae, occludentes, singular, zonula, occludens, multiprotein, junctional, complexes, whose, canonical, function, prevent, leakage, solutes, water, seals, between, epithelial, cells, they, also, play, criti. Tight junctions also known as occluding junctions or zonulae occludentes singular zonula occludens are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epithelial cells 1 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 Tight junctionDiagram of Tight junctionDetailsIdentifiersLatinjunctio occludensMeSHD019108THH1 00 01 1 02007FMA67397Anatomical terminology edit on Wikidata Contents 1 Structure 2 Functions 3 Classification 4 See also 5 References 6 External linksStructure EditTight 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 Thus tight junctions join together the cytoskeletons of adjacent cells nbsp Depiction of the transmembrane proteins that make up tight junctions occludin claudins and JAM proteins Transmembrane proteins Occludin was the first integral membrane protein to be identified It has a molecular weight of 60kDa It consists of four transmembrane domains and both the N terminus and the C terminus of the protein are intracellular It forms two extracellular loops and one intracellular loop These loops help regulate paracellular permeability 4 Occludin also plays a key role in cellular structure and barrier function 5 Claudins were discovered after occludin and are a family of over 27 different members in mammals 6 They have a molecular weight of 20kDa They have a structure similar to that of occludin in that they have four transmembrane domains and similar loop structure They are understood to be the backbone of tight junctions and play a significant role in the tight junction s ability to seal the paracellular space 7 Junctional Adhesion Molecules JAM are part of the immunoglobulin superfamily They have a molecular weight of 40 to 48 kDa 8 Their structure differs from that of the other integral membrane proteins in that they only have one transmembrane domain instead of four It helps to regulate the paracellular pathway function of tight junctions and is also involved in helping to maintain cell polarity 9 Angulins were discovered in 2011 by visual screening of proteins which localize at tricellular tight junctions 10 There are three members of angulins Angulin 1 LSR Angulin 2 ILDR1 and Angulin 3 ILDR2 Similar to JAMs angulins are single transmembrane proteins All angulins have one immunoglobulin like domain in the extracellular region and one PDZ binding motif at the carboxy terminus They are responsible for establishment of tricellular tight junctions and regulate the paracellular barrier function 11 Functions EditThey perform vital functions 12 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 Tight junctions prevent the passage of molecules and ions through the space between plasma membranes of adjacent cells so materials must actually enter the cells by diffusion or active transport in order to pass through the tissue 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 13 The constrained intracellular pathway exacted by the tight junction barrier system allows precise control over which substances can pass through a particular tissue Tight junctions play this role in maintaining 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 is proposed large slit breaks formed by infrequent discontinuities in the TJ complex and numerous small circular pores 14 Tight junctions help to 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 specialised functions of apical and basolateral membranes Classification EditEpithelia are classed as tight or leaky depending on the ability of the tight junctions to prevent water and solute movement 15 Tight epithelia have tight junctions that prevent most movement between cells Examples of tight epithelia include the distal convoluted tubule the collecting duct of the nephron in the kidney and the bile ducts ramifying through liver tissue Other examples are the blood brain barrier and the blood cerebrospinal fluid barrier Leaky epithelia do not have these tight junctions or have less complex tight junctions For instance the tight junction in the kidney proximal tubule a very leaky epithelium has only two to three junctional strands and these strands exhibit infrequent large slit breaks nbsp TEM of negatively stained proximal convoluted tubule of Rat kidney tissue at a magnification of 55 000x and 80 kV with Tight junction Note that the three dark lines of density correspond to the density of the protein complex and the light lines in between correspond to the paracellular space See also EditCadherin Gap junction Tight junction protein disambiguation Zonulin Adherens junctionReferences Edit a b 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 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 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 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 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 amp Therapeutics 18 8 609 615 doi 10 1111 j 1755 5949 2012 00340 x ISSN 1755 5930 PMC 6493516 PMID 22686334 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 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 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 Luissint Anny Claude Artus Cedric 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 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 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 Department Biology Tight Junctions and other cellular connections Davidson College Retrieved 2015 01 12 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 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 Department Biology Tight Junctions and other cellular connections Davidson College Retrieved 2013 09 20 External links Edit nbsp Wikimedia Commons has media related to Tight junctions An Overview of the Tight Junction at Zonapse Net Occludin in Focus at Zonapse Net Tight Junctions at the U S National Library of Medicine Medical Subject Headings MeSH Histology image 20502loa Histology Learning System at Boston University Retrieved from https en wikipedia org w index php title Tight junction amp oldid 1165858069, wikipedia, wiki, book, books, library,
