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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration.
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.
Afiliación
  • Song Y; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: songy2@email.chop.edu.
  • Li D; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Farrelly O; Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Miles L; The Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Li F; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Kim SE; Departments of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Lo TY; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Wang F; Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Li T; Departments of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Thompson-Peer KL; Departments of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Gong J; Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Murthy SE; Department of Neuroscience, The Scripps Research Institute, Howard Hughes Medical Institute, La Jolla, CA 92037, USA.
  • Coste B; Department of Neuroscience, The Scripps Research Institute, Howard Hughes Medical Institute, La Jolla, CA 92037, USA.
  • Yakubovich N; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Patapoutian A; Department of Neuroscience, The Scripps Research Institute, Howard Hughes Medical Institute, La Jolla, CA 92037, USA.
  • Xiang Y; Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Rompolas P; Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Jan LY; Departments of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of Californ
  • Jan YN; Departments of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of Californ
Neuron ; 102(2): 373-389.e6, 2019 04 17.
Article en En | MEDLINE | ID: mdl-30819546
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 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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regeneración / Axones / Proteínas de Drosophila / Canales Iónicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2019 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regeneración / Axones / Proteínas de Drosophila / Canales Iónicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2019 Tipo del documento: Article