The role of rab proteins in neuronal cells and in the trafficking of neurotrophin receptors.
The role of rab proteins in neuronal cells and in the trafficking of neurotrophin receptors.
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DOI：
10.3390/membranes4040642
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发表时间：
2014-10-06
期刊：
影响因子：
4.2
通讯作者：
Cogli L
中科院分区：
文献类型：
--
作者：
Bucci C;Alifano P;Cogli L
神经营养因子是一类对神经元发育、神经元存活和神经元功能非常重要的蛋白质家族。神经营养因子通过结合其受体发挥作用，受体酪氨酸激酶的Trk家族（TrkA、TrkB和TrkC）和肿瘤坏死因子（TNF）受体超家族的成员p75 NTR。神经营养因子与受体的结合触发一系列复杂的信号转导事件，其能够诱导神经元分化，但也负责神经元维持和神经元功能。Rab蛋白是定位于特定细胞内区室的胞质表面的小GTP酶，并且参与控制囊泡转运。Rab蛋白作为膜运输网络的主要调节剂，在神经营养因子受体的运输和信号传导途径中起着核心作用。轴突运输是神经元的致命弱点，因为分子、细胞器，特别是神经营养素-受体复合物必须覆盖长距离。事实上，轴突运输的改变，特别是神经营养素受体的轴突运输的改变是几种人类神经退行性疾病的原因，例如亨廷顿病、阿尔茨海默病、肌萎缩性侧索硬化症和某些形式的夏科-马里-图思病。在这篇综述中，我们将讨论Rab蛋白和神经营养因子受体运输之间的联系及其对下游信号通路的影响。
Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC) and p75NTR, a member of the tumor necrosis factor (TNF) receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways.