The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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 Ca 2+ -permeable non-selective cation channel, functions as an intrinsic inhibitor for axon regeneration in Drosophila. DmPiezo activation during axon regeneration induces local Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)373-389.e6
JournalNeuron
Volume102
Issue number2
DOIs
StatePublished - Apr 17 2019
Externally publishedYes

Keywords

  • axon regeneration
  • corneal sensory nerve
  • dendritic arborization neurons
  • Drosophila
  • ion channels
  • mammalian injury model
  • mechanosensitive
  • nitric oxide synthase
  • Piezo

ASJC Scopus subject areas

  • Neuroscience(all)

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