The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration
Department of Neurobiology; Graduate School of Biomedical Sciences, Program in Neuroscience; Yang Xiang Lab
Amino Acids, Peptides, and Proteins | Cellular and Molecular Physiology | Enzymes and Coenzymes | Nervous System | Neuroscience and Neurobiology
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.
Drosophila, Piezo, axon regeneration, corneal sensory nerve, dendritic arborization neurons, ion channels, mammalian injury model, mechanosensitive, nitric oxide synthase
DOI of Published Version
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
Song, Yuanquan; Wang, Fei; Gong, Jiaxin; Xiang, Yang; and Jan, Yuh Nung, "The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration" (2019). Neurobiology Publications and Presentations. 241.