Neurotrophin-5: A novel neurotrophic factor that activates trk and trkB
Abstract
In vertebrates, the formation and maintenance of neuronal connections are subject to regulation by multiple target-derived, diffusible (neurotrophic) factors. Here we describe the identification and characterization of a novel neurotrophic factor designated neurotrophin-5 (NT-5). NT-5 is structurally related to nerve growth factor and is expressed in embryonic as well as adult tissues. Recombinant NT-5 promotes the survival of peripheral sensory and sympathetic neurons and induces differentiation of the pheochromocytoma cell line PC12. NT-5 activates two trk-related tyrosine kinase receptors and shares these receptors with other neurotrophins. Activation of multiple receptors may permit a single neurotrophin to control target innervation by distinct neuronal populations. Receptor sharing could enable neurotrophic factors emanating from distinct targets to cooperate in regulating neurons with multiple connections.
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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 [22]
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- Authors
- Berkemeier, L. R., Winslow, J. W., Kaplan, D. R., Nikolics, K., Goeddel, D. V., & Rosenthal, A.
- Affiliations
- Genentech (US)
- Frederick National Laboratory for Cancer Research (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1991-11
- Volume
- 7
- Issue
- 5
- Pages
- 857-866
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2080880626
- Cited by
- 836
- References
- 60
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 1 · 2018: 6 · 2017: 10 · 2016: 9 · 2015: 7 · 2014: 18 · 2013: 9 · 2012: 10
- FWCI
- 36.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01co074101-034)
- National Cancer Institute (N01 CO-74101)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- neurotrophin-5, neurotrophic factors, Trk receptors, TrkB receptor, receptor tyrosine kinase, nerve growth factor, peripheral sensory neurons, sympathetic neurons, neuronal survival, neuronal innervation, target innervation
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, DNA, Gene Expression Regulation, Humans, Membrane Proteins, Molecular Sequence Data, Nerve Growth Factors, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Recombinant Proteins, Receptor, Ciliary Neurotrophic Factor, Receptor, trkA, Rats
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