Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK; Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Semin Cell Dev Biol. 2014 Mar;27:32-43. doi: 10.1016/j.semcdb.2013.10.004. Epub 2013 Oct 27.
Neurons are highly polarised cells. They make contact with their targets through long axons, along which a steady flux of proteins, lipids, nucleic acids and organelles is constantly maintained. This process is crucial to the development and maintenance of the nervous system, as proven by the many neurodegenerative disorders associated with defective axonal transport. Specific pools of endocytic organelles, which travel along the axon towards the cell body, have assumed a growing importance by virtue of their transported signals. These organelles, named signalling endosomes, vehicle growth factors, such as neurotrophins, and their signalling receptors all the way from the axon terminals to the neuronal cell body. Due to the central importance of neurotrophins in neuronal development and survival, significant efforts have gone over the years into the study of long-range neutrophin trafficking and signalling. Recent evidence has pointed to a role of signalling endosomes in the axonal retrograde transport of many morphogenetic and survival factors, increasing their importance even further. In light of these findings, signalling endosomes have shown potential for integration of different growth factors signals and the ability to decode them by differential sorting in the neuronal cell body. In this review we aim to discuss the state of the field regarding the nature and dynamics of signalling endosomes, their signalling capabilities, their energy requirements for axonal transport and last but not least, their importance in health and disease.
神经元是高度极化的细胞。它们通过长长的轴突与靶细胞接触，沿着轴突不断维持着蛋白质、脂质、核酸和细胞器的稳定流动。这个过程对神经系统的发育和维持至关重要，许多与轴突运输缺陷相关的神经退行性疾病就证明了这一点。由于其运输的信号，特定的内吞细胞器池沿着轴突向细胞体移动，其重要性日益增加。这些细胞器被命名为信号内体，它们将生长因子（如神经营养因子）及其信号受体从轴突末端运输到神经元细胞体。由于神经营养因子在神经元发育和存活中的核心重要性，多年来人们一直在努力研究长距离神经营养因子的运输和信号转导。最近的证据表明，信号内体在许多形态发生和存活因子的轴突逆行运输中起作用，这进一步增加了它们的重要性。鉴于这些发现，信号内体已经显示出整合不同生长因子信号的潜力，并具有通过在神经元细胞体中进行差异分拣来解码它们的能力。在这篇综述中，我们旨在讨论关于信号内体的性质和动力学、信号转导能力、它们在轴突运输中的能量需求以及最后但同样重要的是它们在健康和疾病中的重要性的研究现状。
