Ephrin-A5

Ephrin-A5 is a is_associated_with::protein that in humans is encoded by the EFNA5 is_associated_with::gene.

Ephrin-A5 is a is_associated_with::glycosylphosphatidylinositol (GPI)-anchored protein of the ephrin-A subclass of ephrin ligands that binds to the EphA subclass of is_associated_with::Eph receptors. 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 is_associated_with::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 is_associated_with::growth cones in cultures of mouse spinal is_associated_with::motor neurons. Interestingly, 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 is_associated_with::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 is_associated_with::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 is_associated_with::retinal ganglion cells to distinct regions in the is_associated_with::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 is_associated_with::anterior SC.