When external EphA receptors bind to ephrinAs, the latter are also known to signal back into their own cell, but they elicit growth cone expansion rather than collapse. As with EphA receptors, this effect depended on the separation of EphA and ephrinA. Both EphrinA and EphA can thus act as guidance receptors on the same growth cone, with opposite results.
Decreased sensitivity to external ligand or receptors might be achieved naturally by regulated colocalization. The resulting desensitization might allow, for example, several axons that express both EphA and ephrinA to grow out as a bundle without repelling each other.