自噬
突触可塑性
细胞生物学
突触后电位
生物
原肌球蛋白受体激酶B
神经科学
神经退行性变
PI3K/AKT/mTOR通路
非突触性可塑性
长时程增强
脑源性神经营养因子
神经营养因子
变质塑性
信号转导
受体
生物化学
医学
内科学
细胞凋亡
疾病
作者
Vassiliki Nikoletopoulou,Kyriaki Sidiropoulou,Emmanouela Kallergi,Yannis Dalezios,Nektarios Tavernarakis
出处
期刊:Cell Metabolism
[Elsevier]
日期:2017-07-01
卷期号:26 (1): 230-242.e5
被引量:198
标识
DOI:10.1016/j.cmet.2017.06.005
摘要
Autophagy is crucial for neuronal integrity. Loss of key autophagic components leads to progressive neurodegeneration and structural defects in pre- and postsynaptic morphologies. However, the molecular mechanisms regulating autophagy in the brain remain elusive. Similarly, while it is widely accepted that protein turnover is required for synaptic plasticity, the contribution of autophagy to the degradation of synaptic proteins is unknown. Here, we report that BDNF signaling via the tropomyosin receptor kinase B (TrkB) and the phosphatidylinositol-3' kinase (PI3K)/Akt pathway suppresses autophagy in vivo. In addition, we demonstrate that suppression of autophagy is required for BDNF-induced synaptic plasticity and for memory enhancement under conditions of nutritional stress. Finally, we identify three key remodelers of postsynaptic densities as cargo of autophagy. Our results establish autophagy as a pivotal component of BDNF signaling, which is essential for BDNF-induced synaptic plasticity. This molecular mechanism underlies behavioral adaptations that increase fitness in times of scarcity.
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