Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in xenopus ovary
Abstract
Evolutionary conservation of members of the NGF family in vertebrates was studied by DNA sequence analysis of PCR fragments for NGF, BDNF, and NT-3 from human, rat, chicken, viper, Xenopus, salmon, and ray. The results showed that the three factors are highly conserved from fishes to mammals. Phylogenetic trees reflecting the evolution and speciation of the members of the NGF family were constructed. In addition, the gene for a fourth member of the family, neurotrophin-4 (NT-4), was isolated from Xenopus and viper. The NT-4 gene encodes a precursor protein of 236 amino acids, which is processed into a 123 amino acid mature NT-4 protein with 50%-60% amino acid identity to NGF, BDNF, and NT-3. The NT-4 protein was shown to interact with the low affinity NGF receptor and elicited neurite outgrowth from explanted dorsal root ganglia with no and lower activity in sympathetic and nodose ganglia, respectively. Northern blot analysis of different tissues from Xenopus showed NT-4 mRNA only in ovary, where it was present at levels over 100-fold higher than those of NGF mRNA in heart.
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NT-3 and NT-4 were identified by sequence similarity to NGF and BDNF.
“The first neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were discovered through their ability to support the survival of neurons and neurites during development15–17; other members of the neurotrophin family, neurotrophin-3 (NT-3)18–20 and neurotrophin-4 (NT-4)21–23 were then identified through sequence similarity to NGF and BDNF.”
From Neuronal plasticity and neurotrophic factors in drug responses (2017) · cites this paper as [21]
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Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain
Gibon, J., & Barker, P. A. (2017) · The Neuroscientist · doi:10.1177/1073858417697037 · Cited by 115 · see citing works
Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer’s Disease
Forsell, P., Parrado Fernández, C., Nilsson, B., Sandin, J., Nordvall, G., & Segerdahl, M. (2024) · Pharmaceuticals · doi:10.3390/ph17080997 · Cited by 14 · see citing works
- Authors
- Hallböök, F., Ibáñez, C. F., & Persson, H.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1991-05
- Volume
- 6
- Issue
- 5
- Pages
- 845-858
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2119628780
- Cited by
- 834
- References
- 97
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 9 · 2017: 8 · 2016: 8 · 2015: 9 · 2014: 21 · 2013: 11 · 2012: 6
- FWCI
- 41.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2p50ns009199-26a1)
- National Institute on Aging (AG04418, P01AG004418)
- National Institute of Neurological Disorders and Stroke (NS09199)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- neurotrophins, neurotrophin-4, nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, low-affinity NGF receptor, neurite outgrowth, dorsal root ganglia, evolutionary conservation, phylogenetic analysis, gene isolation, ligand-receptor interactions
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Chickens, Biological Evolution, Female, Molecular Sequence Data, Nerve Growth Factors, Nerve Tissue Proteins, Ovary, Rats, Inbred Strains, RNA, Messenger, Salmon, Skates, Fish, Snakes, Protein Biosynthesis, Xenopus, Gene Expression, Rats
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