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神经营养因子通过 Trk 受体的运输机制。

Mechanisms of neurotrophin trafficking via Trk receptors.

机构信息

Department of Biology, Johns Hopkins University, 3400 N. Charles St, 227 Mudd Hall, Baltimore, MD 21218, USA.

Department of Biology, Johns Hopkins University, 3400 N. Charles St, 227 Mudd Hall, Baltimore, MD 21218, USA.

出版信息

Mol Cell Neurosci. 2018 Sep;91:25-33. doi: 10.1016/j.mcn.2018.03.013. Epub 2018 Mar 27.

Abstract

In neurons, long-distance communication between axon terminals and cell bodies is a critical determinant in establishing and maintaining neural circuits. Neurotrophins are soluble factors secreted by post-synaptic target tissues that retrogradely control axon and dendrite growth, survival, and synaptogenesis of innervating neurons. Neurotrophins bind Trk receptor tyrosine kinases in axon terminals to promote endocytosis of ligand-bound phosphorylated receptors into signaling endosomes. Trk-harboring endosomes function locally in axons to acutely promote growth events, and can also be retrogradely transported long-distances to remote cell bodies and dendrites to stimulate cytoplasmic and transcriptional signaling necessary for neuron survival, morphogenesis, and maturation. Neuronal responsiveness to target-derived neurotrophins also requires the precise axonal targeting of newly synthesized Trk receptors. Recent studies suggest that anterograde delivery of Trk receptors is regulated by retrograde neurotrophin signaling. In this review, we summarize current knowledge on the functions and mechanisms of retrograde trafficking of Trk signaling endosomes, and highlight recent discoveries on the forward trafficking of nascent receptors.

摘要

在神经元中,轴突末梢和细胞体之间的长距离通讯是建立和维持神经回路的关键决定因素。神经营养因子是突触后靶组织分泌的可溶性因子,可逆行控制支配神经元的轴突和树突的生长、存活和突触发生。神经营养因子与轴突末梢中的 Trk 受体酪氨酸激酶结合,促进配体结合的磷酸化受体内吞进入信号内体。携带 Trk 的内体在轴突中局部发挥作用,急性促进生长事件,也可以逆行运输到远距离的细胞体和树突,刺激神经元存活、形态发生和成熟所需的细胞质和转录信号。神经元对靶源性神经营养因子的反应还需要新合成的 Trk 受体的精确轴突靶向。最近的研究表明,Trk 受体的顺行运输受逆行神经营养因子信号的调节。在这篇综述中,我们总结了逆行运输 Trk 信号内体的功能和机制的最新知识,并强调了对新生受体正向运输的最新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ab9/6128733/9ab2c040e48a/nihms957745f1.jpg

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