Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Mizui T,Ishikawa Y,Kumanogoh H,Lume M,Matsumoto T,Hara T,Yamawaki S,Takahashi M,Shiosaka S,Itami C,Uegaki K,Saarma M,Kojima Mdoi
10.1073/pnas.1422336112subject
Has Abstractpub_date
2015-06-09 00:00:00pages
E3067-74issue
23eissn
0027-8424issn
1091-6490pii
1422336112journal_volume
112pub_type
杂志文章abstract::To address devastating environmental crises and to improve human well-being, China has been implementing a number of national policies on payments for ecosystem services. Two of them, the Natural Forest Conservation Program (NFCP) and the Grain to Green Program (GTGP), are among the biggest programs in the world becau...
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