Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila.
Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila.
复制标题
DOI：
10.1038/s41467-023-42306-2
复制
发表时间：
2023-10-14
影响因子：
16.6
通讯作者：
Song, Yuanquan
中科院分区：
文献类型：
--
作者：
Trombley, Shannon;Powell, Jackson;Guttipatti, Pavithran;Matamoros, Andrew;Lin, Xiaohui;O'Harrow, Tristan;Steinschaden, Tobias;Miles, Leann;Wang, Qin;Wang, Shuchao;Qiu, Jingyun;Li, Qingyang;Li, Feng;Song, Yuanquan
神经元的再生能力受其内在和外在环境的支配。外周和中枢神经元都表现出依赖细胞类型的轴突再生，但其潜在机制尚不清楚。神经胶质细胞为再生提供了必不可少的环境。然而，胶质细胞-神经元信号传递的途径仍未被充分探索。在这里，我们表明，再生的特异性是由切断轴突诱导的钙瞬变决定的，这种钙瞬变是由L型钙通道介导的，构成了苍蝇再生神经元的核心内在机制。外周神经胶质细胞通过三层平衡的方式调节轴突再生。神经胶质细胞源性肿瘤坏死因子通过其神经元受体在损伤后维持钙通道的表达。神经胶质细胞通过内向整流钾通道(Irk1)增强膜超极化，维持钙通道开放。神经胶质细胞还释放腺苷，腺苷通过神经元腺苷受体(ADAR)激活HCN通道(Ih)，抑制钙瞬变。总而言之，我们确定了一个多方面的胶质细胞-神经元耦合，它可以被劫持以促进神经修复。有限的神经元再生是中枢神经系统损伤后恢复的关键障碍。在这里，作者表明，轴突再生是由神经胶质细胞以多层方式调节的，控制着再生依赖的神经元钙通道。
A neuron’s regenerative capacity is governed by its intrinsic and extrinsic environment. Both peripheral and central neurons exhibit cell-type-dependent axon regeneration, but the underlying mechanism is unclear. Glia provide a milieu essential for regeneration. However, the routes of glia-neuron signaling remain underexplored. Here, we show that regeneration specificity is determined by the axotomy-induced Ca2+ transients only in the fly regenerative neurons, which is mediated by L-type calcium channels, constituting the core intrinsic machinery. Peripheral glia regulate axon regeneration via a three-layered and balanced modulation. Glia-derived tumor necrosis factor acts through its neuronal receptor to maintain calcium channel expression after injury. Glia sustain calcium channel opening by enhancing membrane hyperpolarization via the inwardly-rectifying potassium channel (Irk1). Glia also release adenosine which signals through neuronal adenosine receptor (AdoR) to activate HCN channels (Ih) and dampen Ca2+ transients. Together, we identify a multifaceted glia-neuron coupling which can be hijacked to promote neural repair. Limited neuron regeneration is the key barrier to recovery after central nervous system damage. Here, the authors show that axon regeneration is regulated by glia in a multi-layered manner controlling regeneration-dependent neuronal calcium channels.
登录
查看更多内容
影响因子：
9.8
作者：
Hu W;Wang T;Wang X;Han J
通讯作者：
Han J
DOI：
10.1073/pnas.1716470115
发表时间：
2018-09-04
影响因子：
11.1
作者：
Chuang YC;Lee CH;Sun WH;Chen CC
通讯作者：
Chen CC
影响因子：
4.8
作者：
Hidalgo, Patricia;Gonzalez-Gutierrez, Giovanni;Neely, Alan
通讯作者：
Neely, Alan
DOI：
10.1073/pnas.2009224117
发表时间：
2020-11-24
影响因子：
11.1
作者：
Hsu, I-Uen;Linsley, Jeremy W.;Kuwada, John Y.
通讯作者：
Kuwada, John Y.
外侧缰核中的星形胶质细胞 Kir4.1 驱动抑郁症中的神经元爆发
影响因子：
64.8
作者：
Cui, Yihui;Yang, Yan;Hu, Hailan
通讯作者：
Hu, Hailan