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脑源性神经营养因子的树突翻译与定位机制

Mechanism of the Dendritic Translation and Localization of Brain-derived Neurotrophic Factor.

作者信息

Oe Souichi, Miki Harukata, Nishimura Wataru, Noda Yasuko

机构信息

Division of Anatomy, Bio-imaging and Neuro-cell Science, Jichi Medical University.

出版信息

Cell Struct Funct. 2016 Mar 26;41(1):23-31. doi: 10.1247/csf.15015. Epub 2015 Dec 22.

DOI:10.1247/csf.15015
PMID:26700412
Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor critical for synaptic plasticity, neuronal development and neurite extension. BDNF mRNA is transported to dendrites and axons, where it is expressed locally. We previously reported that dendritic targeting elements in the BDNF 3' UTR are necessary for dendritic transport and interact with cytoplasmic polyadenylation element binding protein 1. Here, we demonstrated that the short 3' UTR directs local translation of BDNF and that locally synthesized BDNF exists in a novel compartment that does not co-localize with markers of endosomes, endoplasmic reticulum, Golgi or the trans-Golgi network. Further, locally synthesized BDNF vesicles co-localized with Bicaudal-D2 (BicD2), a member of dynein motor complex proteins. Silencing BicD2 significantly reduced BDNF local synthesis in dendrites. These new findings may underlie the mechanism of local neuronal response to environmental stimuli.

摘要

脑源性神经营养因子(BDNF)是一种对突触可塑性、神经元发育和神经突延伸至关重要的神经营养因子。BDNF信使核糖核酸(mRNA)被转运至树突和轴突,并在局部表达。我们之前报道过,BDNF 3'非翻译区(UTR)中的树突靶向元件对于树突运输是必需的,并且与细胞质聚腺苷酸化元件结合蛋白1相互作用。在此,我们证明了短3'UTR指导BDNF的局部翻译,并且局部合成的BDNF存在于一个新的区室中,该区域不与内体、内质网、高尔基体或反式高尔基体网络的标志物共定位。此外,局部合成的BDNF囊泡与动力蛋白运动复合体蛋白成员双尾D2(BicD2)共定位。沉默BicD2显著降低了树突中BDNF的局部合成。这些新发现可能是局部神经元对环境刺激作出反应机制的基础。

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