Ephrin A5 is a protein that in humans is encoded by the EFNA5 gene. [5] [6] [7]
Ephrin A5 is a glycosylphosphatidylinositol (GPI)-anchored protein of the ephrin-A subclass of ephrin ligands that binds to the EphA subclass of Eph receptors. Ephrin A5 has also been shown to bind to the EphB2 receptor. [8]
"Reverse" signaling is one unique property of ephrin ligands that allows for the transmission of an intracellular signal in ephrin-expressing cells that is distinct from the signal transmitted in Eph receptor-expressing cells. Although the mechanism of "reverse" signaling by ephrin-As is not well understood, it is relatively surprising considering that ephrin-A ligands are attached to the cell membrane solely by a GPI linkage and unlike ephrin-Bs, lack a potential intracellular signaling domain. Nonetheless, certain ephrin-A ligands are known to initiate reverse signaling cascades like ephrin A5, which has been shown to stimulate the spreading of growth cones in cultures of mouse spinal motor neurons. [9] Reverse signaling by ephrin A5 was demonstrated to be GPI-dependent as the elimination of all GPI linkages by the application of a phosphatidlyinositol-specific phospholipase C abolished the positive effects of ephrin A5 on growth cone spreading. Additionally, EphA receptors were shown to exert opposite effects on motor neuron growth cones by reducing growth cone size.
This finding that ephrin A5 promotes growth cone survival that is opposite of EphA signaling and mediated directly by ephrin A5 reverse signaling has important implications for axon guidance as it provides a mechanism by which migrating axons expressing EphAs would preferentially avoid ephrin A5 expressing cells and possibly migrate towards cells with lower expression of ephrin A5. [9] This mechanism is in fact the same one that mediates the guidance of retinal ganglion cells to distinct regions in the superior colliculus during the formation of the retinotopic map. High ephrin A5 expression on cells in the posterior region of the SC bind to EphAs expressed in RGCs migrating from the temporal retina, inducing growth cone collapse and repelling these RGCs away from the posterior SC towards a region of low ephrin A5 expression in the anterior SC. [10]
Eph receptors are a group of receptors that are activated in response to binding with Eph receptor-interacting proteins (Ephrins). Ephs form the largest known subfamily of receptor tyrosine kinases (RTKs). Both Eph receptors and their corresponding ephrin ligands are membrane-bound proteins that require direct cell-cell interactions for Eph receptor activation. Eph/ephrin signaling has been implicated in the regulation of a host of processes critical to embryonic development including axon guidance, formation of tissue boundaries, cell migration, and segmentation. Additionally, Eph/ephrin signaling has recently been identified to play a critical role in the maintenance of several processes during adulthood including long-term potentiation, angiogenesis, and stem cell differentiation and cancer.
Ephrins are a family of proteins that serve as the ligands of the eph receptor. Eph receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinases (RTKs).
Ephrin-B2 is a protein that in humans is encoded by the EFNB2 gene.
Ephrin-B1 is a protein that in humans is encoded by the EFNB1 gene. It is a member of the ephrin family. The encoded protein is a type I membrane protein and a ligand of Eph-related receptor tyrosine kinases. It may play a role in cell adhesion and function in the development or maintenance of the nervous system.
EPH receptor A2 is a protein that in humans is encoded by the EPHA2 gene.
Ephrin type-B receptor 4 is a protein that in humans is encoded by the EPHB4 gene.
EPH receptor A4 is a protein that in humans is encoded by the EPHA4 gene.
Ephrin type-B receptor 1 is a protein that in humans is encoded by the EPHB1 gene.
EPH receptor A3 is a protein that in humans is encoded by the EPHA3 gene.
Ephrin type-B receptor 6 is a protein that in humans is encoded by the EPHB6 gene.
Ephrin type-A receptor 8 is a protein that in humans is encoded by the EPHA8 gene.
Ephrin type-A receptor 7 is a protein that in humans is encoded by the EPHA7 gene.
EPH receptor A5 is a protein that in humans is encoded by the EPHA5 gene.
Ephrin A4 is a protein that in humans is encoded by the EFNA4 gene.
Ephrin-A2 is a protein that in humans is encoded by the EFNA2 gene.
Ephrin A3 is a protein that in humans is encoded by the EFNA3 gene.
Ephrin-B3 is a protein that in humans is encoded by the EFNB3 gene.
EPH receptor A1 is a protein that in humans is encoded by the EPHA1 gene.
Ephrin type-B receptor 3 is a protein that in humans is encoded by the EPHB3 gene.
The growth cone is a highly dynamic structure of the developing neuron, changing directionality in response to different secreted and contact-dependent guidance cues; it navigates through the developing nervous system in search of its target. The migration of the growth cone is mediated through the interaction of numerous trophic and tropic factors; netrins, slits, ephrins and semaphorins are four well-studied tropic cues (Fig.1). The growth cone is capable of modifying its sensitivity to these guidance molecules as it migrates to its target; this sensitivity regulation is an important theme seen throughout development.
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