Inhibition of Myelin Membrane Sheath Formation by Oligodendrocyte-derived Exosome-like Vesicles
Inhibition of Myelin Membrane Sheath Formation by Oligodendrocyte-derived Exosome-like Vesicles
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DOI：
10.1074/jbc.m110.190009
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发表时间：
2011-01-07
影响因子：
4.8
通讯作者：
Simons, Mikael
中科院分区：
文献类型：
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作者：
Bakhti, Mostafa;Winter, Christine;Simons, Mikael
髓磷脂的形成是一个多步骤的过程，由许多不同的细胞外因子控制。在中枢神经系统（CNS）发育过程中，少突胶质细胞祖细胞分化为成熟的少突胶质细胞，在接受轴突或其微环境的适当信号后，开始用髓鞘膜鞘包裹轴突。启动这一过程所需的信号是未知的。在这里，我们发现少突胶质细胞分泌小的膜囊泡，外泌体样囊泡，进入细胞外空间，抑制少突胶质细胞的形态分化和髓鞘的形成。外泌体样囊泡的抑制作用被肌动球蛋白收缩性抑制剂所阻止。重要的是，当细胞在条件神经元培养基中孵育时，少突胶质细胞的外泌体样囊泡的分泌显著减少。总之，我们的研究结果为细胞外空间的小而可扩散的少突胶质来源的囊泡载体具有抑制细胞生长的特性提供了新的证据。我们提出神经元控制自身抑制性少突胶质源性外泌体的分泌，以协调髓鞘膜的生物发生。
Myelin formation is a multistep process that is controlled by a number of different extracellular factors. During the development of the central nervous system (CNS), oligodendrocyte progenitor cells differentiate into mature oligodendrocytes that start to enwrap axons with myelin membrane sheaths after receiving the appropriate signal(s) from the axon or its microenvironment. The signals required to initiate this process are unknown. Here, we show that oligodendrocytes secrete small membrane vesicles, exosome-like vesicles, into the extracellular space that inhibit both the morphological differentiation of oligodendrocytes and myelin formation. The inhibitory effects of exosome-like vesicles were prevented by treatment with inhibitors of actomyosin contractility. Importantly, secretion of exosome-like vesicles from oligodendrocytes was dramatically reduced when cells were incubated by conditioned neuronal medium.In conclusion, our results provide new evidence for small and diffusible oligodendroglial-derived vesicular carriers within the extracellular space that have inhibitory properties on cellular growth. We propose that neurons control the secretion of autoinhibitory oligodendroglial-derived exosomes to coordinate myelin membrane biogenesis.