ArticleThe EMBO journal1995
Functional analysis of mutant neurotrophins deficient in low-affinity binding reveals a role for p75LNGFR in NT-4 signalling.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 130 citations in OpenAlex.
- Neurotrophins and Their Receptors: BDNF's Role in GABAergic Neurodevelopment and Disease.International journal of molecular sciences · 2024Review
- Revisiting the expression of BDNF and its receptors in mammalian development.Frontiers in molecular neuroscience · 2023Article
- Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression.Scientific reports · 2021Article
- Neurotrophin-4 is more potent than brain-derived neurotrophic factor in promoting, attracting and suppressing geniculate ganglion neurite outgrowth.Developmental neuroscience · 2012Article
- Understanding proneurotrophin actions: Recent advances and challenges.Developmental neurobiology · 2010Review
- Proneurotrophin-3 is a neuronal apoptotic ligand: evidence for retrograde-directed cell killing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Design of a conformationally defined and proteolytically stable circular mimetic of brain-derived neurotrophic factor.The Journal of biological chemistry · 2008Article
- Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function.Neuroscience · 2007Article
- Low concentrations of aggregated beta-amyloid induce neurite formation via the neurotrophin receptor p75.Journal of molecular medicine (Berlin, Germany) · 2005Article
- Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury.Molecular neurobiology · 2003Review
- Predominant neuronal B-cell loss in L5 DRG of p75 receptor-deficient mice.Journal of anatomy · 2002Article
- Nerve growth factor plays a divergent role in mediating growth of rat C6 glioma cells via binding to the p75 neurotrophin receptor.Journal of neuro-oncology · 2002Article
- Neurotrophins: roles in neuronal development and function.Annual review of neuroscience · 2001Review
- Regulation of neurotrophin signaling in aging sensory and motoneurons: dissipation of target support?Molecular neurobiology · 2000Review
- The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.Protein science : a publication of the Protein Society · 1999Article
- The interaction of neurotrophins with the p75NTR common neurotrophin receptor: a comprehensive molecular modeling study.Protein science : a publication of the Protein Society · 1999Article
- Selective regulation of trkC expression by NT3 in the developing peripheral nervous system.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1999Article
- TrkB isoforms with distinct neurotrophin specificities are expressed in predominantly nonoverlapping populations of avian dorsal root ganglion neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1999Article
- Regulation of neurotrophin receptor expression by retinoic acid in mouse sympathetic neuroblasts.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1999Article
- TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1998Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neurotrophins mediate their effects through binding to two classes of receptors, a tyrosine kinase receptor, member of the Trk family, and the low-affinity neurotrophin receptor, p75LNGFR, of as yet undefined signalling capacity. The need for a two-component receptor system in neurotrophin signalling is still not understood. Using site-directed mutagenesis, we have identified positively charged surfaces in BDNF, NT-3 and NT-4 that mediate binding to p75LNGFR. Arg31 and His33 in NT-3, and Arg34 and Arg36 in NT-4, located in an exposed hairpin loop, were found to be essential for binding to p75LNGFR. In BDNF, however, positively charged residues critical for p75LNGFR binding (Lys95, Lys96 and Arg97) were found in a spatially close but distinct loop region. Models of each neurotrophin were built using the coordinates of NGF. Analysis of their respective electrostatic surface potentials revealed similar clusters of positively charged residues in each neurotrophin but with differences in their precise spatial locations. Disruption of this positively charged interface abolished binding to p75LNGFR but not activation of cognate Trk receptors or biological activity in Trk-expressing fibroblasts. Unexpectedly, loss of low-affinity binding in NT-4, but not in BDNF or NT-3, affected receptor activation and biological activity in neuronal cells co-expressing p75LNGFR and TrkB, suggesting a role for p75LNGFR in regulating biological responsiveness to NT-4. These findings reveal a possible mechanism of ligand discrimination by p75LNGFR and suggest this receptor may selectively modulate the biological actions of specific neurotrophin family members.
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