Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity.
Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity.
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DOI：
10.1083/jcb.201606052
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Parkinson DB
中科院分区：
文献类型：
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作者：
Mindos T;Dun XP;North K;Doddrell RD;Schulz A;Edwards P;Russell J;Gray B;Roberts SL;Shivane A;Mortimer G;Pirie M;Zhang N;Pan D;Morrison H;Parkinson DB
PNS 中雪旺细胞的再生能力是损伤后功能修复的基础。在这项研究中，Mindos 等人。显示肿瘤抑制因子 Merlin 和 Hippo/YAP 信号在损伤后生成具有修复能力的雪旺细胞中的新功能。 Merlin 肿瘤抑制因子的缺失和 Hippo 信号通路的激活在细胞增殖和肿瘤发生的控制中发挥着重要作用。我们已经确定了 Merlin 和 Hippo 通路效应器 Yes 相关蛋白 (YAP) 在控制雪旺细胞 (SC) 可塑性和损伤后周围神经修复中的全新作用。周围神经系统 (PNS) 损伤会导致 SC 分子表型发生巨大变化，并产生具有修复能力的 SC，从而指导功能修复。我们发现这些细胞中 Merlin 的缺失会导致 PNS 中轴突再生和髓鞘再生的灾难性失败。这种效应是通过激活 Merlin 缺失 SC 中的 YAP 表达来介导的，YAP 的缺失可以恢复轴突的再生和功能修复。这项工作确定了控制 SC 再生潜力的新机制，并为理解 PNS 中功能性神经修复的正确控制提供了新的见解。
The regenerative capacity of Schwann cells in the PNS underlies functional repair after injury. In this study, Mindos et al. show a new function for the tumor suppressor Merlin and Hippo/YAP signaling in the generation of repair-competent Schwann cells after injury. Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS.