NEUROTROPHIN-6 IS A NEW MEMBER OF THE NERVE GROWTH-FACTOR FAMILY

DURING vertebrate development, many neurons depend for survival and di fferentiation on their target cells(1-3). The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF)(1). NGF and the other known members of the neurotrophin f amily, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are conserved as distinct genes over la rge evolutionary distances(4-6). Here we report the cloning of neurotr ophin-6 (NT-6), a new member of this family from the teleost fish Xiph ophorus. NT-6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producin g cells. The addition of heparin (but not chondroitin) effects the rel ease of NT-6 from cell surface and extracellular matrix molecules. Rec ombinant purified NT-6 has a spectrum of actions similar to NGF on chi ck sympathetic and sensory neurons, albeit with a lower potency. NT-6 is expressed in the embryonic valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding mo lecules may modulate its action in the nervous system.