Ephrin A5 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''EFNA5''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Ephrin A5 is a
glycosylphosphatidylinositol
Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in ...
(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 rec ...
s. Ephrin A5 has also been shown to bind to the
EphB2 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
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
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 cone
A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ram� ...
s in cultures of mouse spinal
motor neurons.
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.
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 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 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.
References
Further reading
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External links
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{{Growth factor receptor modulators