Ephrin A5 is a
protein that in humans is encoded by the ''EFNA5''
gene.
Ephrin A5 is a
glycosylphosphatidylinositol (GPI)-anchored protein of the ephrin-A subclass of
ephrin ligands that binds to the EphA subclass of
Eph receptor
Eph receptors (Ephs, after erythropoietin-producing human hepatocellular 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 r ...
s. Ephrin A5 has also been shown to bind to the
EphB2
Ephrin type-B receptor 2 is a protein that in humans is encoded by the ''EPHB2'' gene.
Function
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their stru ...
receptor.
Reverse signaling in growth cone survival
"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 neuron
A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectl ...
s.
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
Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...
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.
Formation of the retinotopic map
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
Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they mana ...
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.
This mechanism is in fact the same one that mediates the guidance of
retinal ganglion cell
A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the human eye, eye. It receives visual information from photoreceptor cell, photoreceptors via two intermediate neuron typ ...
s to distinct regions in the
superior colliculus
In neuroanatomy, the superior colliculus () is a structure lying on the roof of the mammalian midbrain. In non-mammalian vertebrates, the homologous structure is known as the optic tectum, or optic lobe. The adjective form ''tectal'' is commonly ...
during the formation of the
retinotopic
Retinotopy (from Greek τόπος, place) is the mapping of visual input from the retina to neurons, particularly those neurons within the visual stream. For clarity, 'retinotopy' can be replaced with 'retinal mapping', and 'retinotopic' with 'r ...
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
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...
SC.
References
Further reading
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External links
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{{Growth factor receptor modulators