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Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution

Please always quote using this URN: urn:nbn:de:bvb:20-opus-61703
  • Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fi.sh Xiphophorus, with the mammalian homlogues. Genomic clones encoding fish NGFMammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fi.sh Xiphophorus, with the mammalian homlogues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purifi.ed recombinant BDNF. However, the activity ofrecombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng,lml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63% and 90% identity, respectively, indicating that NGF bad reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates ftom a common ancestral gene about 600 million years ago. By RNA gel blot anaJysis NGF mRNA was detected during late embryonie development; BDNF was present in adult brain.show moreshow less

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Metadaten
Author: Rudolf Götz, Friedrich Raulf, Manfrad Schartl
URN:urn:nbn:de:bvb:20-opus-61703
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Year of Completion:1992
Source:In: Journal of Neurochemistry (1992) , 59, 432-442
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
GND Keyword:Physiologische Chemie
Tag:Brain-derived neurotrophic factor; Fish; Nerve growth factor; Neuronal survival; Recombinant protein expression
Release Date:2011/12/09
Licence (German):License LogoDeutsches Urheberrecht