Ephrin

Is a family of receptors which are activated ephrin receptor (EPHS) in response to the binding ephrin. The formation EPHS a subfamily known receptor tyrosine kinase of maximum (of RTK). Its ligand both EPHS is a membrane-bound proteins that require direct cell-cell interaction of Eph receptor activation of ephrin. Axonal guidance formation of tissue boundaries, cell migration, and includes segmentation, Eph / ephrin signaling is involved in the regulation of various processes important for embryonic development. Further, the long term potentiation, angiogenesis, and Ephemeris / epherin signaling plays an important role in the maintenance of several processes in adults including cancer and differentiation of stem cells has recently been found.

Ephrin

EPHS will be divided (encoded by a gene locus were identified EPHB and EPHA, respectively) to EphBs two subclasses, and EphA class based on the through-bound ephrin or glycol linked ephrin ligand, or binding affinity and its sequence similarity B ligand can be. Eph receptors of the 16 identified in animals (see above), a human-expressing (EphB6 and EphB1-4) 5 EphBs and (EphA10 and EphA1-8) 9 EphA kind are known. Overall, it binds the ephrin all of subclasses in priority, but we, EPHS a subclass that did not cross-linked with ephrin in opposition to the subset of most. It was proposed that could be due to different binding mechanisms recently intrasubclass specific Eph / ephrin binding is used by EphBs EphA and such a part. Exceptions intrasubclass binding specificity observed in EPHS that can be activated to bind EphA4 Noto ephrin-A5 which activates ephrin-B3 are bonded recently and EPHB2 is as shown, there are, however . EPHA / ephrinA reaction, good EPHB / ephrin-B interactions may be due to the fact usually that are interconnected to require small structural changes in ephrin Volume partially mechanisms “key and keyhole”, Unlike those used for mechanism “Fit induced” requires more energy to change the conformation of EphBs will be coupled to the observation ephrin-BS with higher affinity, EphA kind EphBs.

Extracellular domain of Eph receptors is formed spherical ephrin ligand binding domain that is highly conserved, of two fibronectin type III domain cysteine-rich region. Cytoplasmic domain of Eph receptors, is composed of a juxtamembrane region of the PDZ binding motif tyrosine residues two conserved tyrosine kinase domain, sterile α and motif (SAM). Is converted to its active form, the intracellular tyrosine kinase after binding of ephrin ligands, inhibiting downstream activation or to the extracellular domain of becoming serine residues and phosphorylation juxtamembrane domain Eph receptor tyrosine spherical, of Ephesus You can You can be the signaling cascade.

The segmentation by the body is divided into functional units for the first basic process of embryogenesis, has been found in all vertebrates and vertebrate most. Essential for future functional differentiation and – in the region of the divided embryo, cells begin to show boundaries morphological and biochemical behavior of the cells is being dramatically different. The segmentation of the hindbrain, is a specific process. However proximal mesoderm, it is adaptive adjustment process development according to Riyabodei growth and dynamic. Eph receptors are ephrin different and, are represented in these areas, Effects signaling to be important in development and maintenance of the proper boundaries of the sector in which they are known by functional analysis. The similar study carried out in zebrafish, segment containing a representation of the striped pattern of the ligand and Eph receptor is essential for proper segmentation, which shows the process of segmentation, such as this – expressions that are interrupted , or misplaced leading to border of absence.

Model of neural connections are established by molecular driver that has received the (Axon Guide) signal directly axon on the order of road or trail the nervous system to develop. The Eph / ephrin signaling, reducing the survival rate mainly, by migrating repel from quote axon from Eph / ephrin activation, growth cone of the axon to regulate the migration of axons to the target destination. This mechanism to repel axons to migrate through the reduction of viable growth cone, because it depends on the relative levels of expression of ephrins and Eph, indicates the migration of axonal growth cone based on the relative levels of these to, the expression of ephrin and Eph allow the slope of the ephrin and Eph expression in target cells. EPHB receptors mediate growth cone collapse while inducing the survival of growth cone of ephrin-AB and reverse ephrin signaling and usually EPHA forward signaling.

Ability of signaling to induce axons to migrate to Ephesus / Efurin’epeso / ephrin expression gradient is resolved, lead to the development of neural map, visual map retina system of gradual level of expression of both ephrin ligand and receptor Ephesians (for a detailed description of Ephesus / ephrin signaling,) it has been demonstrated in the formation please refer to the “acquisition of the retina map” in the ephrin. By forming a barrier between the lobes and hippocampus such, further studies have shown the role of Eph in topographic areas of other central nervous system such as learning and memory.
In addition to the formation of topographic maps, Eph / ephrin signaling is involved in the correct orientation of the axons of motor neurons of the spinal cord. Contribute to neuronal guidance engine several members of the ephrin and EPHS, but by starting to axon to EPHA expression transition, ephrin A5 reverse signaling of the repulsive force of the migration mediated growth cone and growth cones of motor neuron can play an important role in survival is shown.

Eph / ephrin signaling, cells of several types of axons of neurons in target destinations during the development of the central nervous system – plays an important role in cell-mediated migration. Axon will control the direction of the nerve axons by their ability to inhibit the survival of the growth cone of the axon to repel migrating away from Ephesus / ephrin active site Eph / ephrin signaling. Rather than react to absolute levels of ephrin and EPHS in cells has been with us simply, growth cones of axons migration, relative level of ephrin expression can migrate the axons expressing the EPHS and Ephesians ephrin not going to, corresponding to is indicated by the slope of the ephrin and Eph-expressing cells to the destination survival of growth cone of the axon is not suppressed completely. Are associated with survival, a decrease in general, activation of ephrin is dependent Ephesus on the growth of survival cone recent rebound in growth cone migration axon – Ephesians “forward”, rather than the activation of ephrin It turns out that it is not the only effect of various signaling but signaling “reverse” of the ephrin ligand to the survival of growth cone or Eph receptor.

Formation of retinal maps organizational is properly migrated axons of retinal ganglion cells in the retina of a specific region in SC mediated by the gradient of Ephesus superior colliculus (SC) (cover under vertebrate following view) ( ephrin formula in both the RGC of the transition leaving the retina and SC RGC) of is required. The decrease in the survival of the growth cone of the axon of the above, the slope from the temporary area of ​​expression retina at high levels EPHA receptor to target the SC front and from the front ephrin ligand expression back high to low in the SC, the RGC from nose retina with EPHA low expression to their final destination in the rear SC that allows you to tell the RGC axons of migratory birds,. Similarly, the gradient of ephrin-B1 expression to indicate the transition of RGC side of the ventral EPHB expression and back side of each medium and SC in the middle-ventral axis of the HC.

The unique properties of one of the ephrin ligand is you can start a signal of “reverse” are distinguished from intracellular signaling to activate cells expressing the Eph receptor and another many of them. The ephrin-BS and ephrin-AS, mechanism of signal to mediate cellular responses that differ from those associated with the activation of the receptors, each of the “reverse”, as shown takes place fully Although it is not understood. More specifically, ephrin A5, to stimulate the growth cone distribution of spinal motor neurons is shown, ephrin-B1, to promote the maturation of dendritic is shown.