A 13.1-kilodalton protein, cysteine-rich neurotrophic factor (CRNF), w
as purified from the mollusk Lymnaea stagnalis by use of a binding ass
ay on the p75 neurotrophin receptor. CRNF bound to p75 with nanomolar
affinity but was not similar in sequence to neurotrophins or any other
known gene product. CRNF messenger RNA expression was highest in adul
t foot subepithelial cells; in the central nervous system, expression
was regulated by lesion. The factor evoked neurite outgrowth and modul
ated calcium currents in pedal motor neurons. Thus, CRNF may be involv
ed in target-derived trophic support for motor neurons and could repre
sent the prototype of another family of p75 ligands.