Abstract
Neurotrophins are synthesized first as precursors, followed by maturation through proteolytic removal of the "pro" region. Since pro- and mature neurotrophins elicit opposite functional effects by differential interactions with Trks and p75 receptors, extracellular cleavage represents a new way to control the synaptic functions of neurotrophins. A single nucleotide mutation in the pro-region appears to affect synaptic targeting and activity-dependent secretion of BDNF in hippocampal neurons. These results demonstrate new mechanisms by which neurotrophins regulate synaptic plasticity and memory function.
MeSH terms
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Brain-Derived Neurotrophic Factor / metabolism
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Hippocampus / physiology
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Nerve Growth Factors / chemistry
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Nerve Growth Factors / genetics
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Nerve Growth Factors / metabolism*
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Nerve Growth Factors / pharmacology*
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Neuronal Plasticity / physiology
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Neurons / metabolism*
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Point Mutation
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Protein Processing, Post-Translational*
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Receptor, Nerve Growth Factor
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Receptor, trkA / metabolism
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Receptors, Nerve Growth Factor / metabolism
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Synaptic Transmission / drug effects*
Substances
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Brain-Derived Neurotrophic Factor
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Nerve Growth Factors
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor
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Receptor, trkA