Persephin is a secreted protein belonging to the glial cell line-derived neurotrophic factor (GDNF) family of the TGF-b superfamily. It shares 38-46% amino acid (aa) identity with family members GDNF, neurturin and artemin. Persephin is expressed at very low levels in most tissues.1 The 156 aa, 10-12kD mature protein contains a signal sequence, a pro-domain and a 96 aa mature sequence with several cysteines that are conserved among family members. It circulates as an unglycosylated disulfide-linked homodimer. Mature human persephin shares 81% and 80%, 89% and 87% amino acid sequence identity with mouse, rat, cow and dog persephin, respectively. Like other GDNF family members, persephin acts through engagement of GRFa4, a glycosylphosphatidylinositol (GPI)-linked GDNF receptor family (GRF) member that signals through the receptor tyrosine kinase RET. Persephin is reported to promote both the survival and growth of central dopaminergic and motor neurons, and kidney development.1 These effects are correlated with the expression patterns of GFRa4, and RET.2, 3 Functional GFRa4 isoforms are found only in thyroid, adrenal medulla and portions of the central nervous system, and include GPI-linked, transmembrane and soluble forms.3, 4 In vitro, persephin promotes survival only in neurons which coexpress GPI-linked GFRa4 with RET.2, 5 This effect does not show a strong correlation to the recruitment of RET in lipid rafts seen with other GDNF family members.6 Disruption of the persephin gene results in mice that are morphologically normal but have more damage and less effective repair after central nervous system insult that stimulates a stroke. Microinjection of persephin prior to treatment protects against damage in both wild-type and mutant mouse brains, but surprisingly, high doses of persephin are detrimental.7.||A DNA sequence encoding the TGF-b-like domain of human Persephin (Ala 61-Gly 156; Accession # NP_004149) was expressed in E. coli.||Calculated molecular mass of ~ 10.3kD.||Activity: Measured by its ability to stimulate proliferation of TT (medullary thyroid cancer cells) cells.||Storage and Stability:|Lyophilized powder may be stored at 4°C for short-term only. Reconstitute to nominal volume by adding sterile buffer and store at -20°C. Reconstituted product is stable for 12 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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