Gap Junction

The fundamental structural and operational unit of all living things is the cell. Each cell has a cytoplasm that is surrounded by a membrane and is home to a variety of biomolecules, including proteins and nucleic acids.

Cells can develop specialised functions and perform a variety of tasks within the cell, including protein synthesis, DNA repair, replication, and motility. Within the cell, cells can specialise and move around. Due to their small size, the majority of cells are measured in micrometres.

Cell-cell Interaction

The term “cell-cell interaction” describes the physical contact between cell surfaces, which is essential for the growth and operation of multicellular organisms. Cells can communicate with one another through these interactions to react to changes in their surroundings. The cell’s survival depends on its capacity to transmit and receive messages. Stable cell-cell interactions, such as those made through cell junctions, are possible. These junctions let cells within a particular tissue communicate and organise themselves. Others, including those between immune system cells or the connections that cause tissue inflammation, are transitory or short-lived. These interactions between cells are different from others, such as those between cells and the extracellular matrix. Cancer and unregulated cell proliferation may originate from a breakdown in cell communication.

Cell-matrix interaction

Cell-matrix interactions are mediated by adhesion receptors and result in the creation of multi-protein adhesion structures that interact with the actin cytoskeleton at the interior of the cell (CMACs). They are collectively known as cell-matrix adhesion complexes.

These adhesions serve as crucial data processing hubs that allow cells to detect a variety of extracellular signals that contain details on the chemical, geometry, and physical characteristics of the ECM. Mechanosensitive cells communicate this information to subsequent mechanotransduction pathways and signalling cascades to affect a variety of processes, including the cell shape, polarity, fate, motility, and the deposition and/or restructuring of ECM components. The substrate type or chemical composition, its rigidity, and its surface topography influence force-induced events through CMACs.

Cell Junctions

 

Anchoring junctions and tight junctions are the other two types of cell junctions seen in vertebrates. Through proteins attached to the cytoskeleton of the cell, anchoring junctions hold cells together. Epithelial cells, which are cells found on the surface of the body and lining organs, frequently have tight junctions, which are regions where cells are joined very closely together to form a barrier.

While plant cells lack gap junctions, they do have plasmodesmata, which act as conduits to connect the cytoplasm of two nearby plant cells. Plasmodesmata have a different structure than gap junctions because plant cells have strong cell walls, but they serve roughly the same purpose. Through their plasmodesmata, plant cells may communicate with one another and control the movement of tiny chemicals.

Gap Junction

 

Gap junctions are collections of intercellular channels that allow ions and tiny molecules to move directly between cells. Gap junctions are found connecting nearly all cells in solid tissues and were first identified as low-resistance ion channels interconnecting excitable cells (nerve and muscle). Gap-junctional intercellular communication has been adapted to a range of roles with diverse regulation mechanisms according to their long evolutionary history. Hexamers of the medium-sized families of integral proteins connexins in chordates and innexins in precordates make up the gap-junctional channels. By examining mutations in flies, worms, and humans as well as targeted gene disruption in mice, researchers have investigated the roles of gap junctions.

The direct transport of ions and small molecules between adjacent cells is made possible by gap junctions, which are collections of intercellular channels. Hexameric clusters (connexons) of tetraspan integral membrane proteins, the connexins, bind head-to-head to form the intercellular channels (Cx). These channels group together to form polymorphic plaques or maculae that range in size from a few to thousands of units. The tight membrane apposition necessary for connexon docking sterically excludes most other membrane proteins, leaving the junction’s distinctive tiny extracellular “gap” of 2 nm. Prechordates have innexin-based gap junctions. Connexins were created by convergent evolution in chordates and then expanded into a 21-member gene family by gene duplication.

It is unclear if the three pannexins, which are linked to innexins, form intercellular channels, yet they have persisted in vertebrates. Intercellular channels made of either a carboxy-terminal truncation of Cx43 or an M34A mutant of Cx26 have 7Å-resolution electron crystallographic structures available. The Cx26 channel pore has a “plug,” but otherwise the pore morphologies are comparable. Deletion of amino acids 2–7 significantly reduces the density of this plug, indicating that the amino terminus contributes to its structure.

The amino-terminus of Cx26 was seen folded into the channel mouth without producing a plug in a 3.5Å- X-ray crystallographic structure, which is assumed to be a representation of the open channel conformation. A role for the amino-terminus as a gating structure has been supported by the physiological evidence linking it to voltage-gating of the Cx26 and Cx32 channels. However, Cx43 also exhibits voltage-gating, and the mystery behind its lack of a plug-like structure continues to this day. A quarter-worth century of X-ray advancement can be summed up by comparing an intercellular channel structure from 1985 with the 3.5Å structure from 2009.

Gap Junction Structure

Connexin proteins make up gap junctions in the cells of vertebrates. (Gap junctions in invertebrate cells are made up of innexin proteins, which are unrelated to connexin proteins but serve a similar purpose.) A connexon is made up of six connexin groups, and two connexons combined make a channel through which molecules can move. Pannexin proteins make up additional channels in gap junctions. Pannexins were first believed to only create channels within a cell, not across cells, hence they are still relatively poorly understood. In what is referred to as a gap junction plaque, hundreds of channels are discovered together at the location of a gap junction. A mass of proteins makes up a plaque

Function 

Electrically excitable cells, like neurons, the heart, and smooth muscle, depend on the ability of nearby cells to transfer ions through low-resistance routes to function. The characteristics of gap junctions (electrical synapses) for electrical transmission between neighbouring cells led to their discovery in the heart and nerve. When cells are connected by gap junctions, synaptic transmission is accelerated and groups of cells can be synchronised for coordinated electrical and mechanical output.

Almost all of the cells in solid tissues, aside from those that are electrically excitable, are connected by gap junctions. GJIC’s primary job is to distribute metabolic demands among cell groups, which act as a buffer against spatial gradients of nutrients or signalling chemicals. For instance, it has been demonstrated that the targeted deletion of Cx32 in mice causes a lack of sympathetic reactivity, which impairs the mobilisation of glucose from glycogen reserves. Only a portion of the hepatocytes can be directly stimulated by postganglionic sympathetic axons because they terminate at the borders of the liver lobules. It is assumed that second messengers diffuse through gap junctions to indirectly excite the remaining portion of the lobule. To prevent the loss of a vital metabolic enzyme or ion channel in one cell, gap junctions may also act as suppressors of somatic cell mutations. For instance, hypoxanthine phosphoribosyltransferase (HGPRTase), a crucial enzyme in the nucleotide salvage pathway, is compromised, which leads to Lesch-Nyhan syndrome. Impaired HGPRTase causes a rise in phosphoribosyl pyrophosphate levels, a notable acceleration of purine biosynthesis, and an excess generation of urate. Metabolic collaboration, or gap junction creation with normal cells, can metabolically restore mutant fibroblasts from Lesch-Nyhan syndrome patients in cell culture. Furthermore, the absence of symptoms in heterozygous female Lesch-Nyhan carriers is probably explained by metabolic cooperation. Given that HGPRTase resides on the X chromosome, a mosaic of mutant and healthy cells is produced when the X chromosome is randomly inactivated. Individuals are thus asymptomatic as a result of nearby nonmutant cells’ metabolic rescue of mutant cells.

Specialised Function Revealed by Connexin Mutation

Human Mutations

Gap junctions have a lengthy ancestral history in metazoans, thus it is not surprising that they have been modified to perform a wide range of physiological tasks in many cell types. Human mutations and targeted connexin gene deletion in mice have revealed numerous cell- and tissue-specific activities of GJIC. In humans, mutations in Cx47 cause Pelizaeus-Merzbacher-Like-Disease, a central demyelinating disease, and mutations in Cx32 cause X-linked Charcot-Marie-Tooth syndrome, a common peripheral demyelination neuropathy. Mutations in Cx26 cause more than half of all profound hereditary deafness; these illnesses are frequently syndromic and involve skin conditions. Disorders of the epidermis and the auditory system also accompany mutations in Cx31 and Cx30, though they are often less severe. Mutations in the ocular lens-specific genes Cx46 or Cx50, whose expression is primarily localised to the lens of the eye, are frequently linked to familial cataracts. The pleomorphic, syndromic disorder oculodentodigital dysplasia, which affects a variety of cell types, is caused by mutations in the Cx43 gene.

Targeted Mutations in Mice

Targeted connexin mutations in mice have shown a wide range of gap-junction functions in different organs. In many of these situations, a specific connexin fills a specific void, performing a crucial task that cannot be covered by another connexin. For instance, the Cx26 deletion causes the gap junction-coupled syncytiotrophoblast I and II in the labyrinth layer of the placenta to stop transporting glucose, which causes embryonic lethality. The human placenta, in contrast, has a single enormous syncytiotrophoblast and is hence immune to Cx26 mutations. Cx45 deletions are also embryonically fatal; in this example, a cardiac arrhythmia probably occurred just as the heart started to beat. Due to a failure in ovarian follicle formation at the antral stage, Cx37 knockouts are female sterile. A premature restart of meiosis and luteinization is thought to be caused by a lack of connection between the cumulus cells and the oocyte. Heart arrhythmias resembling human right-bundle-branch block are caused by the loss of Cx40, which is common in the His-Purkinje system.

In three different mouse lines, the Cx43 coding sequence was changed to one of the Cx32, Cx40, or Cx26 coding regions. The three connexins were not able to replace Cx43 in all situations, as evidenced by the fact that all three animal lines displayed novel functional abnormalities specific to each connexin. A knockin of Cx31 into the Cx43 locus revealed the pulmonary outflow deficits reported in the Cx43KO animal, despite none of the lines exhibiting the deficiencies. Connexins may therefore perform both distinct and redundant tasks.

Question 1: What is Gap Junction?

Answer:

Cell junctions known as gap junctions join neighbouring cells together via protein channels. Each cell’s cytoplasm is connected by these channels, which permit the movement of chemicals, ions, and electrical signals. Due to the fact that gap junctions exist between every cell that touches another cell directly, the vast majority of cells in the body include them. Red blood cells and sperm cells are two exceptions because they travel and don’t typically come in contact with other cells closely. Plant cells are joined by channels termed plasmodesmata rather than gap junctions, which are only seen in animal cells.

Question 2: In smooth and cardiac muscles, cell junctions are represented by?

Answer:

Direct contact between muscle cells is made possible by gap junctions, which also facilitate electrical transmission. As a result, depolarization waves travel quickly across the entire system as they pass from cell to cell. Gap junctions are present in smooth muscles to enable the same rapid spread of depolarization as in cardiac muscles. There are no cell-cell junctions in skeletal muscle.

Question 3: Name the different cell junctions found in tissue.

Answer:

Different cell junction found in tissue are as follows:

• Tight junction
• Gap junction
• Adhering junction

Question 4: What is a tight junction?

Answer:

Tight junctions, which separate tissue compartments and control the selective transport of solutes across the epithelium, create a continuous intercellular barrier between epithelial cells.

Question 5: What is the main purpose of gap junctions?

Answer:

Gap junctions, which are made up of two unrelated protein families called pannexins and connexins, facilitate the movement of ions, second messengers, and tiny metabolites between adjacent cells.