Tight junction
Encyclopedia
Tight junctions, or zonula occludens, are the closely associated areas of two cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 whose membranes
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex
Cell junction
A cell junction is a type of structure that exists within the tissue of a some multicellular organism . Cell junctions consist of protein complexes and provide contact between neighbouring cells or between a cell and the extracellular matrix...

 present only in vertebrates. The corresponding junctions that occur in invertebrates are septate junctions.

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. Although more proteins are present, the major types are the claudins and the occludin
Occludin
Occludin is a protein that in humans is encoded by the OCLN gene.Occludin is a 65-kDa integral plasma-membrane protein located at the tight junctions, described for the first time in 1993 by Shoichiro Tsukita...

s. These associate with different peripheral membrane proteins located on the intracellular side of plasma membrane, which anchor the strands to the actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

 component of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

. Thus, tight junctions join together the cytoskeletons of adjacent cells.

Functions

They perform vital functions:
  • They hold cells together.
  • Barrier function, which can be further subdivided into protective barriers and functional barriers serving purposes such as material transport and maintenance of osmotic balance:
    • They help to maintain the 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
      Endocytosis
      Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

       at the apical surface and exocytosis
      Exocytosis
      Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

       at the basolateral surface) to be preserved. This aims to preserve the transcellular transport.
    • They prevent the passage of molecules and ions through the space between cells. So materials must actually enter the cells (by diffusion
      Diffusion
      Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...

       or active transport
      Active transport
      Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...

      ) in order to pass through the tissue. This pathway provides control over what substances are allowed through. (Tight junctions play this role in maintaining the blood-brain barrier
      Blood-brain barrier
      The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

      .) 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.


In human physiology there are two main types of epithelia
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 using distinct types of barrier mechanism. Dermal structures such as skin form a barrier from many layers of keratinised squamous cells. Internal epithelia on the other hand more often rely on tight cells junctions for their barrier function. This kind of barriers is mostly formed by only one or two layers of cells. Until recently it was not clear whether tight cell junctions also play any role in the barrier function of the skin and similar external epithelia, recent research suggests that this is indeed the case.

Classification

Epithelia are classed as 'tight' or 'leaky' depending on the ability of the tight junctions to prevent water and solute
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...

 movement:
  • Tight epithelia have tight junctions that prevent most movement between cells. An example of a tight epithelium is the distal convoluted tubule
    Distal convoluted tubule
    The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...

    , and the collecting duct part of the nephron
    Nephron
    The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....

     in the kidney
    Kidney
    The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

    .
  • 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.

See also

  • Cadherin
    Cadherin
    Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

  • Zonulin
    Zonulin
    Zonulin is a protein that participates in tight junctions between cells of the wall of the digestive tract. Initially discovered in 2000 as the target of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae, it has been implicated in the pathogenesis of coeliac disease and diabetes...

  • Gap junction
    Gap junction
    A gap junction or nexus is a specialized intercellular connection between a multitude of animal cell-types. It directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells....



External links

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