Journey of brain-derived neurotrophic factor: from intracellular trafficking to secretion
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Journey of brain-derived neurotrophic factor: from intracellular trafficking to secretion Masami Kojima 1,2,3
&
Chiaki Ishii 4 & Yoshitake Sano 4 & Toshiyuki Mizui 1,2 & Teiichi Furuichi 2,4
Received: 18 June 2020 / Accepted: 7 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Brain-derived neurotrophic factor (BDNF) is known to control a wide variety of brain functions, ranging from memory formation to food intake. However, since the BDNF levels are extremely low in the nervous system, the dynamics in neurons from intracellular trafficking to secretion is absolutely complicated; the understanding is not fully promoted. We here review the findings of those critical mechanisms from intracellular trafficking to the secretion of BDNF. Furthermore, to solve this issue, technological advances for the detection, measurement, and imaging of this growth factor are essential. We believe that this review helps the study of these complex but critical mechanisms of BDNF. Keywords Brain-derived neurotrophic factor . Neurotrophins . Synaptic transmission . BDNF pro-peptide . Ca2+-dependent activator protein for secretion 2 . Exocytosis
The neurotrophin family Neurotrophins (NTs) historically emerged as a family of polypeptides for promoting neuronal survival and differentiation and have recently been studied as a class of modulators for synaptic transmission and plasticity (Bibel and Barde 2000; Park et al. 2008). In the 1950s, the group of Levi-Montalcini and Hamburger found that when a mouse sarcoma tumor was implanted near the spinal cord of the developing chicken the neurons exhibited neurite outgrowth (Levi-Montalcini and Hamburger 1953). The extensive efforts after the finding led to the successful identification of a growth factor namely nerve
* Masami Kojima [email protected] * Teiichi Furuichi [email protected] 1
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan
2
Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012, Japan
3
Graduate School of Frontier Bioscience, Osaka University, Suita 565-0871, Japan
4
Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
growth factor (NGF) (Bocchini and Angeletti 1969; Cohen 1960; Cohen and Levi-Montalcini 1956). Their discovery of NGF played a pioneering role in the studies of developmental neurobiology, which raised a new hypothesis that target-derived secreted proteins control neurite growth and neuronal survival. Over 20 years after the discovery of NGF, Barde et al. (1982) isolated a neuronal survival-eliciting factor from the pig brain, named brain-derived neurotrophic factor (BDNF) (Barde et al. 1982). In 1989, the primary structure of BDNF and its expression in the brain was identified (Leibrock et al. 1989). Interestingly, it was demonstrated that BDNF is highly homologous to NGF at the level of the amino acid sequence, and using a technology of polymerase c
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