Neurotrophin-6 is a new member of the nerve growth factor family.
During vertebrate development, many neurons depend for survival and differentiation on their target cells. The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF). NGF and the other known members of the neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are conserved as distinct genes over large evolutionary distances. Here we report the cloning of neurotrophin-6 (NT-6), a new member of this family from the teleost fish Xiphophorus. NT-6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT-6 from cell surface and extracellular matrix molecules. Recombinant purified NT-6 has a spectrum of actions similar to NGF on chick 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 molecules may modulate its action in the nervous system.
Max-Planck-Institute for Psychiatry, Department of Neurochemistry, Martinsried, Germany.
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R
Götz
R
R
Köster
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C
Winkler
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F
Raulf
F
F
Lottspeich
M
M
Schartl
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H
Thoenen
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D003532:Cyprinodontiformes / Q000196:embryology / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D009414:Nerve Growth Factors; D011509:Proteoglycans; D011994:Recombinant Proteins; C075936:neurotrophin 6; D006493:Heparin