Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in synaptic plasticity. BDNF is initially synthesized as precursor proBDNF, and then the BDNF pro-peptide is simultaneously produced from the precursor protein. The physiological functions of the pro-peptide are largely unknown. Here, Mizui and colleagues demonstrate that the BDNF pro-peptide is a facilitator of hippocampal long-term depression (LTD), requiring the activation of GluN2B-containing NMDA-type receptors and the pan-neurotrophin receptor p75NTR. Second, a common BDNF polymorphism substitutes valine for methionine at amino acid position 66 (Val66Met) in the pro-peptide of BDNF and impairs memory function. Unexpectedly, the pro-peptide with Met mutation completely inhibits hippocampal LTD. These results plus the fact that the Val66Met polymorphism is widespread and shows ethnic differences is important for understanding the role of genetic differences in learning and memory function.
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Mizui T, Ishikawa Y, Kumanogoh H, Lume M, Matsumoto T, Hara T, Yamawaki S, Takahashi M, Shiosaka S, Itami C, Uegaki K, Saarma M and Kojima M: BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met. PNAS [Epub ahead of print, May 26, 2015; doi: 10.1073/pnas.1422336112].
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http://www.pnas.org/content/early/2015/05/22/1422336112