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首页> 外文期刊>Neuron >The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration
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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

机译：机械敏感离子通道压电抑制轴突再生

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摘要

Neurons exhibit a limited ability of repair. Given that mechanical forces affect neuronal outgrowth, it is important to investigate whether mechanosensitive ion channels may regulate axon regeneration. Here, we show that DmPiezo, a Ca2+-permeable non-selective cation channel, functions as an intrinsic inhibitor for axon regeneration in Drosophila. DmPiezo activation during axon regeneration induces local Ca2+ transients at the growth cone, leading to activation of nitric oxide synthase and the downstream cGMP kinase Foraging or PKG to restrict axon regrowth. Loss of DmPiezo enhances axon regeneration of sensory neurons in the peripheral and CNS. Conditional knockout of its mammalian homolog Piezo1 in vivo accelerates regeneration, while its pharmacological activation in vitro modestly reduces regeneration, suggesting the role of Piezo in inhibiting regeneration may be evolutionarily conserved. These findings provide a precedent for the involvement of mechanosensitive channels in axon regeneration and add a potential target for modulating nervous system repair.
机译：神经元表现出有限的修复能力。鉴于机械力影响神经元过度，重要的是研究机械敏离子通道是否可以调节轴突再生。在这里，我们表明DMPIEZO，CA2 + -PERMETEL的非选择性阳离子通道，作为奇孢子虫中轴轴再生的固有抑制剂。轴突再生期间的DMPiezo活化诱导生长锥的局部CA2 +瞬变，导致活化一氧化氮合酶和下游CGMP激酶觅食或PKG以限制轴突再生。 DMPiezo的丧失增强了外周和CNS中的感觉神经元的轴突再生。其哺乳动物同源物的条件敲除在体内加速再生，而其药理学活化在体外谦虚地减少再生，表明压电在抑制再生中的作用可能会被节约地保守。这些发现为轴突再生中的机械敏感通道的参与提供了先例，并添加了用于调节神经系统修复的潜在靶标。

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  • 来源
    《Neuron》 |2019年第2期|共23页
  • 作者

    Song Yuanquan; Li Dan; Farrelly Olivia; Miles Leann; Li Feng; Kim Sung Eun; Lo Tsz Y.; Wang Fei; Li Tun; Thompson-Peer Katherine L.; Gong Jiaxin; Murthy Swetha E.; Coste Bertrand; Yakubovich Nikita; Patapoutian Ardem; Xiang Yang; Rompolas Panteleimon; Jan Lily Yeh; Jan Yuh Nung;

  • 作者单位

    Childrens Hosp Philadelphia Raymond G Perelman Ctr Cellular &

    Mol Therapeut Philadelphia PA;

    Childrens Hosp Philadelphia Raymond G Perelman Ctr Cellular &

    Mol Therapeut Philadelphia PA;

    Univ Penn Dept Dermatol Philadelphia PA 19104 USA;

    Univ Penn Grad Grp Biochem &

    Mol Biophys Philadelphia PA 19104 USA;

    Childrens Hosp Philadelphia Raymond G Perelman Ctr Cellular &

    Mol Therapeut Philadelphia PA;

    Univ Calif San Francisco Howard Hughes Med Inst Dept Physiol San Francisco CA 94158 USA;

    Childrens Hosp Philadelphia Raymond G Perelman Ctr Cellular &

    Mol Therapeut Philadelphia PA;

    Univ Massachusetts Med Sch Dept Neurobiol Worcester MA 01605 USA;

    Univ Calif San Francisco Howard Hughes Med Inst Dept Physiol San Francisco CA 94158 USA;

    Univ Calif San Francisco Howard Hughes Med Inst Dept Physiol San Francisco CA 94158 USA;

    Univ Massachusetts Med Sch Dept Neurobiol Worcester MA 01605 USA;

    Howard Hughes Med Inst Scripps Res Inst Dept Neurosci La Jolla CA 92037 USA;

    Howard Hughes Med Inst Scripps Res Inst Dept Neurosci La Jolla CA 92037 USA;

    Univ Calif San Francisco Dept Biochem &

    Biophys San Francisco CA 94158 USA;

    Howard Hughes Med Inst Scripps Res Inst Dept Neurosci La Jolla CA 92037 USA;

    Univ Massachusetts Med Sch Dept Neurobiol Worcester MA 01605 USA;

    Univ Penn Dept Dermatol Philadelphia PA 19104 USA;

    Univ Calif San Francisco Howard Hughes Med Inst Dept Physiol San Francisco CA 94158 USA;

    Univ Calif San Francisco Howard Hughes Med Inst Dept Physiol San Francisco CA 94158 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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