BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met
| Autor: | Mart Saarma, Toshiyuki Mizui, Haruko Kumanogoh, Tomoya Matsumoto, Sadao Shiosaka, Shigeto Yamawaki, Yasuyuki Ishikawa, Chiaki Itami, Koichi Uegaki, Masami Kojima, Maria Lume, Masami Takahashi, Tomoko Hara |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Tropomyosin receptor kinase B
Biology Hippocampal formation Endocytosis Hippocampus 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Methionine Neurotrophic factors Animals Humans Protein Precursors Receptor 030304 developmental biology Mice Knockout 0303 health sciences Multidisciplinary Polymorphism Genetic Brain-Derived Neurotrophic Factor Long-Term Synaptic Depression Valine Cell biology Rats chemistry nervous system PNAS Plus Synaptic plasticity NMDA receptor Neuroscience 030217 neurology & neurosurgery |
| Popis: | Most growth factors are initially synthesized as precursor proteins and subsequently processed into their mature form by proteolytic cleavage, resulting in simultaneous removal of a pro-peptide. However, compared with that of mature form, the biological role of the pro-peptide is poorly understood. Here, we investigated the biological role of the pro-peptide of brain-derived neurotrophic factor (BDNF) and first showed that the pro-peptide is expressed and secreted in hippocampal tissues and cultures, respectively. Interestingly, we found that the BDNF pro-peptide directly facilitates hippocampal long-term depression (LTD), requiring the activation of GluN2B-containing NMDA receptors and the pan-neurotrophin receptor p75(NTR). The BDNF pro-peptide also enhances NMDA-induced α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor endocytosis, a mechanism crucial for LTD expression. Thus, the BDNF pro-peptide is involved in synaptic plasticity that regulates a mechanism responsible for promoting LTD. The well-known BDNF polymorphism valine for methionine at amino acid position 66 (Val66Met) affects human memory function. Here, the BDNF pro-peptide with Met mutation completely inhibits hippocampal LTD. These findings demonstrate functional roles for the BDNF pro-peptide and a naturally occurring human BDNF polymorphism in hippocampal synaptic depression. |
| Databáze: | OpenAIRE |
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