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TrkB 含有的自噬体通过衔接蛋白 AP-2 的逆行转运介导神经元复杂性并防止神经退行性变。

Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration.

机构信息

Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.

NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.

出版信息

Nat Commun. 2017 Apr 7;8:14819. doi: 10.1038/ncomms14819.

DOI:10.1038/ncomms14819
PMID:28387218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5385568/
Abstract

Autophagosomes primarily mediate turnover of cytoplasmic proteins or organelles to provide nutrients and eliminate damaged proteins. In neurons, autophagosomes form in distal axons and are trafficked retrogradely to fuse with lysosomes in the soma. Although defective neuronal autophagy is associated with neurodegeneration, the function of neuronal autophagosomes remains incompletely understood. We show that in neurons, autophagosomes promote neuronal complexity and prevent neurodegeneration in vivo via retrograde transport of brain-derived neurotrophic factor (BDNF)-activated TrkB receptors. p150/dynactin-dependent transport of TrkB-containing autophagosomes requires their association with the endocytic adaptor AP-2, an essential protein complex previously thought to function exclusively in clathrin-mediated endocytosis. These data highlight a novel non-canonical function of AP-2 in retrograde transport of BDNF/TrkB-containing autophagosomes in neurons and reveal a causative link between autophagy and BDNF/TrkB signalling.

摘要

自噬体主要介导细胞质蛋白或细胞器的周转，以提供营养并清除受损的蛋白质。在神经元中，自噬体在远端轴突中形成，并逆行运输与溶酶体融合在胞体中。虽然神经元自噬的缺陷与神经退行性变有关，但神经元自噬体的功能仍不完全清楚。我们表明，在神经元中，自噬体通过脑源性神经营养因子（BDNF）激活的 TrkB 受体的逆行运输来促进神经元的复杂性并预防体内的神经退行性变。p150/dynactin 依赖性运输含有 TrkB 的自噬体需要它们与内吞作用衔接蛋白 AP-2 的结合，AP-2 是一种先前被认为仅在网格蛋白介导的内吞作用中发挥作用的必需蛋白复合物。这些数据突出了 AP-2 在神经元中 BDNF/TrkB 含有自噬体逆行运输中的新型非典型功能，并揭示了自噬与 BDNF/TrkB 信号之间的因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/3b857af01c9d/ncomms14819-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/c49b1b71488e/ncomms14819-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/fda9118feb70/ncomms14819-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/dcc4f37a5d60/ncomms14819-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/73b7c6c92e3e/ncomms14819-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/d6819340b027/ncomms14819-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/25d81c886e45/ncomms14819-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/3b857af01c9d/ncomms14819-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/c49b1b71488e/ncomms14819-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/fda9118feb70/ncomms14819-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/dcc4f37a5d60/ncomms14819-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/73b7c6c92e3e/ncomms14819-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/d6819340b027/ncomms14819-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/25d81c886e45/ncomms14819-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2760/5385568/3b857af01c9d/ncomms14819-f7.jpg

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