Tight junction

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Tight junction_table_infobox_0

Tight junctionTight junction_header_cell_0_0_0
DetailsTight junction_header_cell_0_1_0
IdentifiersTight junction_header_cell_0_2_0
LatinTight junction_header_cell_0_3_0 junctio occludensTight junction_cell_0_3_1
MeSHTight junction_header_cell_0_4_0 Tight junction_cell_0_4_1
THTight junction_header_cell_0_5_0 Tight junction_cell_0_5_1
FMATight junction_header_cell_0_6_0 Tight junction_cell_0_6_1

Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens) are multiprotein junctional complexes whose general function is to prevent leakage of transported solutes and water and seals the paracellular pathway. Tight junction_sentence_0

Tight junctions may also serve as leaky pathways by forming selective channels for small cations, anions, or water. Tight junction_sentence_1

Tight junctions are present mostly in vertebrates (with the exception of Tunicates). Tight junction_sentence_2

The corresponding junctions that occur in invertebrates are septate junctions. Tight junction_sentence_3

Structure Tight junction_section_0

Tight junctions are composed of a branching network of sealing strands, each strand acting independently from the others. Tight junction_sentence_4

Therefore, the efficiency of the junction in preventing ion passage increases exponentially with the number of strands. Tight junction_sentence_5

Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly. Tight junction_sentence_6

There are at least 40 different proteins composing the tight junctions. Tight junction_sentence_7

These proteins consist of both transmembrane and cytoplasmic proteins. Tight junction_sentence_8

The three major transmembrane proteins are occludin, claudins, and junction adhesion molecule (JAM) proteins. Tight junction_sentence_9

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. Tight junction_sentence_10

Thus, tight junctions join together the cytoskeletons of adjacent cells. Tight junction_sentence_11

Transmembrane proteins: Tight junction_sentence_12

Tight junction_unordered_list_0

  • 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. Occludin also plays a key role in cellular structure and barrier function.Tight junction_item_0_0
  • Claudins were discovered after occludin and are a family of 24 different mammalian proteins. 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. Different claudins are found in different locations throughout the human body.Tight junction_item_0_1
  • Junction Adhesion Molecules (JAM) are part of the immunoglobulin superfamily. They have a molecular weight of ~40kDa. Their structure differs from that of the other integral membrane proteins in that they only have one transmembrane protein instead of four. It helps to regulate the paracellular pathway function of tight junctions and is also involved in helping to maintain cell polarity.Tight junction_item_0_2

Functions Tight junction_section_1

They perform vital functions: Tight junction_sentence_13

Tight junction_unordered_list_1

  • They hold cells together.Tight junction_item_1_3
  • 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 junction_item_1_4
    • Tight junctions 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 at the apical surface and exocytosis at the basolateral surface) to be preserved. This aims to preserve the transcellular transport.Tight junction_item_1_5
    • 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. 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.Tight junction_item_1_6

In human physiology there are two main types of epithelia using distinct types of barrier mechanism. Tight junction_sentence_14

Epidermal structures such as skin form a barrier from many layers of keratinized squamous cells. Tight junction_sentence_15

Internal epithelia on the other hand more often rely on tight junctions for their barrier function. Tight junction_sentence_16

This kind of barrier is mostly formed by only one or two layers of cells. Tight junction_sentence_17

It was long unclear whether tight cell junctions also play any role in the barrier function of the skin and similar external epithelia but recent research suggests that this is indeed the case. Tight junction_sentence_18

Classification Tight junction_section_2

Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement: Tight junction_sentence_19

Tight junction_unordered_list_2

  • 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 barrierTight junction_item_2_7
  • 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.Tight junction_item_2_8

See also Tight junction_section_3

Tight junction_unordered_list_3

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Tight junction.