Binding of brain-derived neurotrophic factor to the nerve growth factor receptor

doi:10.1016/0896-6273(90)90107-Q

Neuron

Volume 4, Issue 4, April 1990, Pages 487-492

https://doi.org/10.1016/0896-6273(90)90107-Q Get rights and content

Abstract

The neurotrophic proteins BDNF and NGF are related in their primary structures, and both have high- and low-affinity receptors on their responsive neurons. In this study, we investigate the extent to which these receptors can discriminate between BDNF and NGF. We found that a 1000-fold excess of the heterologous ligand is needed to reduce binding to the high-affinity receptor by 50%, but that the same concentrations of BDNF and NGF similarly reduce the binding of either ligand to the low-affinity receptor. Results obtained with cells transfected with the low-affinity NGF receptor gene indicate that these cells bind BDNF, in addition to NGF, whereas cells before transfection do not. These data indicate that the low-affinity NGF receptor is also a low-affinity BDNF receptor and that whatever is conferring high-affinity binding and biological response also considerably reinforces the ability of the low-affinity receptor to discriminate between NGF and BDNF.

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Neurotrophins are a family of secreted proteins that promote different activities during development and in the adult nervous system, like cell survival and differentiation, synaptic plasticity, and axonal growth. In mammals, only four neurotrophin genes encoding for nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 4 are sufficient to modulate these functions in the peripheral and central nervous systems and in nonneuronal organs. This chapter will provide an overall view of the evolution, mechanisms, signaling, and function of the neurotrophins and their receptors, not only in the nervous system, and their role in several human pathologies.
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Citation Excerpt :
Other variants have associated with differential localization for specific translation – long 3′ segments, for instance, localizes BDNF to dendrites (Lau et al., 2010). BDNF interacts primarily with two cellular receptors (Fig. 2), tropomyosin-related kinase B (TrkB) receptor (Huang and Reichardt, 2003) and p75 neutrophin receptor (p75NTR) (Rodriguez-Tebar et al., 1990). TrkB binds with high affinity and specificity to BDNF and neurotrophin-4 (NT-4).
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^∗: Present address: Cajal Institute of Neurobiology, Doctor Arce 37, E-28002 Madrid Spain.

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ArticleBinding of brain-derived neurotrophic factor to the nerve growth factor receptor

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Binding of brain-derived neurotrophic factor to the nerve growth factor receptor