Title

The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

UMMS Affiliation

Department of Neurobiology; Graduate School of Biomedical Sciences, Program in Neuroscience; Yang Xiang Lab

Publication Date

2019-04-17

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cellular and Molecular Physiology | Enzymes and Coenzymes | Nervous System | Neuroscience and Neurobiology

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.

Keywords

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

DOI of Published Version

10.1016/j.neuron.2019.01.050

Source

Neuron. 2019 Apr 17;102(2):373-389.e6. doi: 10.1016/j.neuron.2019.01.050. Epub 2019 Feb 25. Link to article on publisher's site

Journal/Book/Conference Title

Neuron

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30819546

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