α-synuclein transfer through tunneling nanotubes occurs in SH-SY5Y cells and primary brain pericytes from Parkinson's disease patients.
α-synuclein transfer through tunneling nanotubes occurs in SH-SY5Y cells and primary brain pericytes from Parkinson's disease patients.
复制标题
DOI：
10.1038/srep42984
复制
发表时间：
2017-02-23
影响因子：
4.6
通讯作者：
Curtis MA
中科院分区：
文献类型：
--
作者：
Dieriks BV;Park TI;Fourie C;Faull RL;Dragunow M;Curtis MA
帕金森病(PD)的特征是存在被称为路易小体的包涵体，主要由α-突触核蛋白(α-SYN)聚集体组成。越来越多的证据表明，α-SYN在非神经细胞中自我繁殖，从而促进了帕金森病在脑内的发展和扩散。隧道纳米管(TNT)是一种细长的、基于F-肌动蛋白的膜通道，连接细胞，已被认为是细胞间α-SYN转移的管道。SH-SY5Y细胞和原代人脑周细胞来自死后的帕金森病大脑，经常形成TNT，允许α-SYN转移和细胞之间的长距离电耦合。周细胞原位含有α-SYN沉淀物，就像神经元中看到的那样。通过TNTs的交换是快速的，但取决于蛋白质的大小。蛋白质能够在TNTs连接的细胞网络中传播。通过TNTs的转移不限于α-SYN；荧光控制蛋白和标记膜也通过TNTs交换。最重要的是，TNTs的形成和转移在有丝分裂过程中继续进行。总之，我们的结果提供了SH-SY5Y细胞和人脑PD周细胞中TNT的详细描述，证明了它们在α-SYN转移中的作用，并进一步强调了非神经细胞，如周细胞在疾病进展中的重要性。
Parkinson’s disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of α-synuclein (α-syn) aggregates. There is growing evidence that α-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for α-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow α-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain α-syn precipitates like those seen in neurons. Exchange through TNTs was rapid, but dependent on the size of the protein. Proteins were able to spread throughout a network of cells connected by TNTs. Transfer through TNTs was not restricted to α-syn; fluorescent control proteins and labeled membrane were also exchanged through TNTs. Most importantly the formation of TNTs and transfer continued during mitosis. Together, our results provide a detailed description of TNTs in SH-SY5Y cells and human brain PD pericytes, demonstrating their role in α-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression.