@article{c7c89aa07da44e738698566ec6a5cdcb,
title = "The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration",
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",
author = "Yuanquan Song and Dan Li and Olivia Farrelly and Leann Miles and Feng Li and Kim, {Sung Eun} and Lo, {Tsz Y.} and Fei Wang and Tun Li and Thompson-Peer, {Katherine L.} and Jiaxin Gong and Murthy, {Swetha E.} and Bertrand Coste and Nikita Yakubovich and Ardem Patapoutian and Yang Xiang and Panteleimon Rompolas and Jan, {Lily Yeh} and Jan, {Yuh Nung}",
note = "Funding Information: We thank S. Younger, J. Mathur, T. Cheng, W. Zhang, and J. Goldshteyn for technical assistance; P.H. O'Farrell for advice on the Nos pathway and comments for the manuscript; S. Kune, M. Eddison, M. Sokolowski, S. Davies, Y. Guo, M. Freeman, Z. Ma, and A. Sheehan for fly lines; Bloomington Stock Centre and VDRC for fly stocks; J. Wood for plasmids; the Neurons R Us Culture Service Center of PTNC at the University of Pennsylvania for providing cultured neurons; the Krishna P. Singh Center for Nanotechnology at the University of Pennsylvania for supporting the microfluidic device; members of the Jan lab and Song lab for helpful discussions. Y.S. is a recipient of the National Institute of Neurological Disorders and Stroke (NINDS) Pathway to Independence Award. This work was supported by an IDDRC New Program Development Award (CHOP/Penn), an NINDS K99/R00 award (5K99NS088211-02 and R00NS088211), and an NIH grant (1R01NS107392-01) to Y.S. and NIH grants (2R37NS040929 and R35NS097227) to Y.N.J. A.P. L.Y.J. Y.N.J. are investigators of Howard Hughes Medical Institute. Conceptualization, Y.S. D.L. S.E.K. and Y.N.J.; Methodology, Y.S. D.L. and P.R.; Investigation, Y.S. D.L. O.F. L.M. F.L. T.L. T.Y.L. K.L.T.-P. S.E.M. and B.C.; Formal Analysis, F.W. and Y.X.; Writing – Original Draft, Y.S. Y.N.J. and L.Y.J.; Writing – Review & Editing, P.R. Y.X. and A.P.; Funding Acquisition, Y.S. Y.N.J. and L.Y.J.; Resources, J.G. and N.Y.; Supervision, Y.S. P.R. and Y.N.J. The authors declare no competing interests. Funding Information: We thank S. Younger, J. Mathur, T. Cheng, W. Zhang, and J. Goldshteyn for technical assistance; P.H. O{\textquoteright}Farrell for advice on the Nos pathway and comments for the manuscript; S. Kune, M. Eddison, M. Sokolowski, S. Davies, Y. Guo, M. Freeman, Z. Ma, and A. Sheehan for fly lines; Bloomington Stock Centre and VDRC for fly stocks; J. Wood for plasmids; the Neurons R Us Culture Service Center of PTNC at the University of Pennsylvania for providing cultured neurons; the Krishna P. Singh Center for Nanotechnology at the University of Pennsylvania for supporting the microfluidic device; members of the Jan lab and Song lab for helpful discussions. Y.S. is a recipient of the National Institute of Neurological Disorders and Stroke (NINDS) Pathway to Independence Award. This work was supported by an IDDRC New Program Development Award (CHOP/Penn), an NINDS K99/R00 award ( 5K99NS088211-02 and R00NS088211 ), and an NIH grant ( 1R01NS107392-01 ) to Y.S., and NIH grants ( 2R37NS040929 and R35NS097227 ) to Y.N.J. A.P., L.Y.J. Y.N.J. are investigators of Howard Hughes Medical Institute . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = apr,
day = "17",
doi = "10.1016/j.neuron.2019.01.050",
language = "English (US)",
volume = "102",
pages = "373--389.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}