Persephin is a disulfide-linked homodimer neurotrophic factor structurally related to GDNF (glial cell line-derived neurotrophic factor), Artemin, and Neurturin. These proteins belong to the cysteine-knot family of growth factors that assume stable dimeric structures. Persephin signals through a multicomponent receptor system, composed of RET and one of four GFRα (α1-α4) receptors. The GFRα4 was first identified in chicken and was later shown to be the preferential binding subunit for Persephin. Persephin promotes the survival of ventral midbrain dopaminergic neurons and motor neurons after sciatic nerve axotomy, and like GNDF, promotes ureteric bud branching. Recombinant murine Persephin is a disulfide-linked homodimer, composed of two 10.3 kDa polypeptide chains (96 total amino acid residues). Each chain contains seven conserved cysteine residues, one of which (Cys 63) is used for inter-chain disulfide bridging and the others are involved in intramolecular ring formation known as the cysteine knot configuration. Persephin is one of the GDNF family ligands and belongs to transforming growth factor β (TGF-β) superfamily.
In contrast to GDNF (glial cell line-derived neurotrophic factor) and neurturin, persephin does not support survival of peripheral neurons. Persephin induces differentiation of mesencephalic dopaminergic neurons.
