Oligodendrocytes support axonal transport and maintenance via exosome secretion.
Oligodendrocytes support axonal transport and maintenance via exosome secretion.
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DOI：
10.1371/journal.pbio.3000621
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发表时间：
2020-12
期刊：
影响因子：
9.8
通讯作者：
Krämer-Albers EM
中科院分区：
文献类型：
--
作者：
Frühbeis C;Kuo-Elsner WP;Müller C;Barth K;Peris L;Tenzer S;Möbius W;Werner HB;Nave KA;Fröhlich D;Krämer-Albers EM
神经元延伸需要维护的长轴突，并且容易退化。轴突的长期完整性依赖于内在机制，包括轴突运输和来自邻近胶质细胞的外在支持。髓鞘形成的少突胶质细胞对下面轴突的支持机制只被部分理解。少突胶质细胞释放具有外泌体性质的细胞外囊泡（EV），其在递送至神经元后改善体外神经元活力。在这里，我们表明，少突胶质细胞外泌体分泌受损2小鼠突变体表现出继发性轴突变性，由于少突胶质细胞特异性基因缺陷。野生型少突胶质细胞外泌体通过改善营养缺乏神经元的代谢状态和促进轴突运输来支持神经元。突变的少突胶质细胞释放较少的外泌体，这些外泌体共享代表性不足的蛋白质的共同特征。值得注意的是，突变的外泌体缺乏支持营养缺乏的神经元和促进轴突运输的能力。总之，这些发现表明，胶质细胞到神经元外泌体转移促进神经元的长期维护，促进轴突运输，提供了一种新的机制之间的联系髓鞘疾病和继发性丧失轴突完整性。神经元轴突的长期完整性取决于内在机制，如轴突运输和来自相邻胶质细胞的外在支持。这项研究表明，神经胶质细胞中影响轴突完整性的遗传缺陷会损害少突胶质细胞外泌体的分泌及其支持营养缺乏的神经元和促进轴突运输的能力。
Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligodendroglial exosome secretion is impaired in 2 mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wild-type oligodendroglial exosomes support neurons by improving the metabolic state and promoting axonal transport in nutrient-deprived neurons. Mutant oligodendrocytes release fewer exosomes, which share a common signature of underrepresented proteins. Notably, mutant exosomes lack the ability to support nutrient-deprived neurons and to promote axonal transport. Together, these findings indicate that glia-to-neuron exosome transfer promotes neuronal long-term maintenance by facilitating axonal transport, providing a novel mechanistic link between myelin diseases and secondary loss of axonal integrity. The long-term integrity of neuronal axons depends on intrinsic mechanisms such as axonal transport and on extrinsic support from adjacent glial cells. This study shows that genetic defects in glia that affect axonal integrity impair the secretion of oligodendrocyte exosomes and their ability to support nutrient-deprived neurons and promote axonal transport.
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影响因子：
3.6
作者：
Bury LA;Sabo SL
通讯作者：
Sabo SL
DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
2.1
作者：
Ghasemi A;Zahediasl S
通讯作者：
Zahediasl S
影响因子：
30.8
作者：
Lappe-Siefke, C;Goebbels, S;Nave, KA
通讯作者：
Nave, KA
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin