Tight junction
n., plural: tight junctions
[taɪt/ ˈdʒʌŋkʃən]
Definition: a protein complex between two cells that creates a seal to prevent any leakage of the content through the cell membranes
Table of Contents
What are tight junctions? Tight junctions are the intercellular barrier between two neighboring endothelial and epithelial cell membranes that creates a selectively permeable barrier that exhibits charge and size specificity for material transport. Also, known as zonula occludens, tight junctions are basically a protein complex between two cells that creates a seal to prevent any leakage of the content through the cell membranes.
Cell-to-cell junctions are specialized junctions between cells of animal tissues. They are formed by multiprotein complexes that provide contact between adjacent cells or between a cell and the extracellular matrix.
Apart from tight junctions, three other major types of junctions are adhering junctions, gap junctions, and anchoring junctions (e.g. desmosomes). Let’s learn more about tight junction definition, structure, function, and more!
Tight Junctions Definition
As the name suggests, tight junctions are the junctions or the seal or joint between two cells in the epithelial membrane. In simple words, these are tight cell junctions that prevent leakage.
Tight junctions (also called zonula occludens or occluding junctions) are a type of cell junction characterized by forming an adhesion complex between two neighboring cells serving as a tight seal between the cells. The tight junctions are essentially a protein complex between two cells.
The tight junction or the seal prevents the leakage of content and controls the paracellular transport and permeability. Thus, tight junctions create a continuous semipermeable membrane connection in the cellular membrane.
Where are tight junctions found in the body?
These tight junctions are found in endothelial cells and epithelial cell membranes.
Tight junctions function primarily as a barrier or regulator that controls the movement of solutes, and liquids based on their charge and size. The phenomenon of the dependence of transport of material on charge and size is also referred to as perm-selectivity.
Tight junctions are a highly resistant barrier that is critical for several physiological cellular functions. The cellular membrane of different organs exhibits a varied range of tight junction permeability.
Accordingly, tight junctions can be ‘tight’ or ‘leaky’. The leaky tight junctions permit the movement of a large amount of material across them and are thus referred to posses low Trans-Epithelial Resistance (TER).
Watch this vid about tight junctions:
Biology definition:
A tight junction is a type of cellular junction formed between adjacent epithelial cells or between adjacent epithelial cells. The outer layers of two adjacent cells fuse, thereby serving as a barrier to the passage of fluid between cells. As a barrier, tight junctions help maintain the polarity of cells and the osmotic balance.
Tight junctions also play a role in maintaining the blood-brain barrier. Apart from serving as a barrier between cells, tight junctions also function as a means to hold cells together. Epithelial cells with tight junctions may be described as tight or leaky depending on the presence and the ability of tight junctions to prevent water and solute movements.
Synonyms: occluding junction; zonula occludens; impermeable cell junction; terminal bar (obsolete)
See also: cell junction, gap junction, desmosome
Tight Junction Structure
Now let us understand the architecture of tight junctions and tight junction components.
A tight junction appears as a junctional complex made up of a branching network made up of sealing strands. These tight junction strands function independently of each other and the number of strands determines the efficiency of the tight junction.
These strands are made up of rows of transmembrane proteins that are rooted in the plasma membrane from one end while the other end is exposed to the extracellular domain. These exposed strands form a network. Thus, there are cytoplasmic proteins as well as transmembrane proteins in each strand.
Approximately 40 junctional proteins are involved in the tight junction strand formation. Primarily, there are three major transmembrane tight junction proteins:
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Occludin:
The size of occludin protein is around ~60-65 kDa. The N- and C-terminus of the occludin protein are intracellular. Also, occludin protein has four transmembrane domains. Occludin protein forms one intracellular loop while two other loops are in extracellular domains. Occludin protein helps to preserve the intercellular epithelial barrier function and regulate cellular permeability. Occludin is thus responsible for distribution and barrier function.
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Claudins:
Claudin protein family consists of around 27 proteins, having sizes around ~20 kDa. Claudin proteins are the backbone of the strands of the tight junction. These proteins are quite similar in transmembrane domains as well as loop structure. Claudin proteins can be differentiated from occludin by the presence of a characteristic W-GLW-C-C residue sequence.
Claudin proteins are responsible for charge specificity in the permeation of material across the membrane and have pores in the size range of ~4Å. Some of the claudins are responsible for creating the barrier i.e., barrier builder while other claudins like claudins 1, -3, -4, -8, -11, -14, and -19 are referred to as tightening claudins as they reduce permeability.
For charge selectivity, cation selectivity is exhibited by Claudin 2 and -10b while anion selectivity is shown by claudin-10a.
What does claudin bind to? Claudin is in binding with occludin protein. Also, the gene expression of claudin protein has a correlation with cancer prognosis as well.
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Junction adhesion molecules JAM proteins:
Junctional adhesion molecules or JAM proteins belong to the immunoglobulin superfamily having a size of around ~40kDa. JAM proteins possess only one transmembrane domain and thus differ from other tight junction strand proteins. JAM proteins are primarily the sealants that keep the neighboring cells adhered to each other. JAM proteins regulate the size specificity in the permeation of material across the membrane. Cingulin is another tight junction protein found in a human cell.
Note it!
Tight junctions may get disrupted during a pathogenic infection leading to a disease condition.
Functions of Tight Junctions
Tight junctions not only serve as a semi-permeable barrier for material transport across the epithelium and endothelium cells, but tight junctions are also critical for a number of physiological functions in cell biology.
The role of tight junctions is primarily as a barrier formation along with the following other functions:
- Tight junctions serve to hold the cells thus having a structural role in the membrane.
- Tight junctions serve as a semi-permeable barrier in the paracellular transport across the epithelium and endothelium membrane.
- Tight junctions help in maintaining cell polarity. Transport across the epithelium is driven by the electrochemical gradient. Tight junctions are responsible for the maintenance of apical-basal polarity.
- Epithelial cells’ tight junctions help to maintain the cellular composition intact and create & maintain different compartments in the body.
- Tight junctions in epithelial cells are also involved in cell signaling, bi-directionally, which is involved in cell growth, cell proliferation, cell differentiation, cell migration, and cell survival.
- Tight junctions are responsible for creating an impermeable barrier in several organs like bbb or blood-brain barrier tight junctions for the maintenance of homeostasis.
- Tight junctions are also responsible for skin barrier, intestinal epithelium barrier, and bladder barrier functions.
Disruption of these barriers may result in pathological conditions like, gastritis, diarrhea, jaundice, dermatitis, cancer cell metastases, hypercalciuria with nephrocalcinosis, edema, and retinopathy. Also, a link between cancer metastasis, and protein pathways and signaling pathways have been identified.
Recent Research findings say…
- In vivo studies in animals suggest that expression of blood-brain barrier tight junction-associated proteins, i.e., bbb ZO 1 tight junction protein (tight junction zo proteins) is reduced in diabetes.
- Some drugs like methotrexate may modulate tight junctions.
Other Cell Junctions
Apart from tight junctions, there are other types of cell junctions as well. These are also referred to as anchoring junctions. There are a number of cells that interact with each other (i.e., cell-cell contacts) and with their extracellular matrix via junctions or cell-matrix junctions.
Apart from tight junctions other cell membrane junctions are adhering junctions (adherens junctions or zonula adherens), desmosomes (macula adherens or anchoring junctions), and gap junctions.
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Adhering junctions
These junctions can be found below the tight junctions. For the formation of adhering junctions, cadherin (a glycoprotein from the two adjacent cells) forms a zipper-like structure in the gap between the two cells.
While inside the cells, microfilaments of actin (or actin cytoskeleton filaments) join together resulting in the formation of epithelial cell adhesion junctions circumferentially around the cell i.e., marginal bands.
Epithelial tight junctions play an important role in the morphogenesis of epithelial cells.
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Desmosomes
What are desmosomes? Desmosomes are responsible for joining two cells. These are commonly found in cells that tend to undergo abrasion like skin cells and cardiac cells, These are made up of glycoproteins namely, desmocollins and demosgleins. Characteristically, these junctions appear as circular spots and not as bands. (Figure 2)
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Gap junctions
Intercellular gap aggregate to form channels that permits the transfer of material from one cell to the other. These are considered to be low resistance pathways for the transfer of the material (Figure 3).
Gap junctions are composed of protein:
- In chordate, protein connexins form gap junctions. Connexin protein serves as a signaling protein helping in cellular communication.
- In pre-chordates, protein innexins form gap junctions
The figure below will provide better clarity and visual understanding of the difference between the three types of intercellular junctions, namely epithelial tight junctions, desmosomes, and gap junctions.
The above figurative representation and the text will help answer questions like what are gap and tight junctions…
All the junctional complexes i.e., tight junctions, gap junctions, adherens junctions, and desomosomes together perform the function of cell-cell interaction through the epithelial apical junctional complex.
How about the invertebrates?
Invertebrates possess septate junctions made up of transmembrane protein occludin in their endothelium.
Classification
Depending upon the organ function, tight junctions can be tight or leaky. The leaky tight junctions permit the movement of a large amount of material across them and are thus referred to posses low Trans-Epithelial resistance (TER). A perfect example of this is the human gastrointestinal tract (GIT).
Human GIT has leaky epithelial junctions throughout the tract, as it has to reabsorb most of the water from the intestinal content. However, the distal colon has intestinal tight junctions where water reabsorption is not required to ascertain the formation of solid stool.
Note it!
Tight junctions are water-tight seals between two adjacent cells. Also, it is not necessary that tight junctions exist between only two adjacent cells. There can be tricellular tight junctions. Tricellular tight junction formation occurs between three neighboring cells.
Answer the quiz below to check what you have learned so far about tight junctions.
References
- Anderson, J. M., & Van Itallie, C. M. (2009). Physiology and function of the tight junction. Cold Spring Harbor perspectives in biology, 1(2), a002584. https://doi.org/10.1101/cshperspect.a002584
- Cummins P. M. (2012). Occludin: one protein, many forms. Molecular and cellular biology, 32(2), 242–250. https://doi.org/10.1128/MCB.06029-11
- Otani, T., & Furuse, M. (2020). Tight Junction Structure and Function Revisited. Trends in cell biology, 30(10), 805–817. https://doi.org/10.1016/j.tcb.2020.08.004
- Vermette, D., Hu, P., Canarie, M. F., Funaro, M., Glover, J., & Pierce, R. W. (2018). Tight junction structure, function, and assessment in the critically ill: a systematic review. Intensive care medicine experimental, 6(1), 37. https://doi.org/10.1186/s40635-018-0203-4
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