The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

Autor: Swetha E. Murthy, Fei Wang, Bertrand Coste, Nikita Yakubovich, Sung-Eun Kim, Olivia Farrelly, Yang Xiang, Feng Li, Panteleimon Rompolas, Tsz Y. Lo, Ardem Patapoutian, Katherine L. Thompson-Peer, Yuanquan Song, Yuh Nung Jan, Leann Miles, Tun Li, Dan Li, Jiaxin Gong, Lily Yeh Jan
Přispěvatelé: Laboratory of Food Microbiology and Food Preservation (LFMFP), Universiteit Gent = Ghent University [Belgium] (UGENT)-Department of Food Safety and Food Quality, Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), University of California-University of California, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Kent State University, Faculty of Bioscience Engineering, Department of Food Safety and Food Quality, Laboratory of Food Microbiology and Food Preservation (LFMFP), Ghent University [Belgium] (UGENT), Chinese Academy of Agricultural Engineering (CAEE), Duke University [Durham], The Scripps Research Institute [San Diego], Tsinghua National Laboratory for Information Science and Technology (TNList), Universiteit Gent = Ghent University (UGENT)-Department of Food Safety and Food Quality, Université Nice Sophia Antipolis (1965 - 2019) (UNS), The Scripps Research Institute [La Jolla, San Diego], Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Coste, Bertrand
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Nervous system
Mechanotransduction
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Regenerative Medicine
Mechanotransduction
Cellular

mammalian injury model
Ion Channels
Mice
0302 clinical medicine
Conditional gene knockout
Psychology
Drosophila Proteins
Axon
ComputingMilieux_MISCELLANEOUS
Mice
Knockout

corneal sensory nerve
nitric oxide synthase
Chemistry
General Neuroscience
Cell biology
Drosophila melanogaster
medicine.anatomical_structure
Neurological
Drosophila
Cognitive Sciences
Mechanosensitive channels
Piezo
Sensory Receptor Cells
Knockout
1.1 Normal biological development and functioning
Growth Cones
Article
mechanosensitive
03 medical and health sciences
Mechanosensitive ion channel
dendritic arborization neurons
Underpinning research
Cyclic GMP-Dependent Protein Kinases
medicine
Animals
Regeneration
Growth cone
Neurology & Neurosurgery
Regeneration (biology)
PIEZO1
axon regeneration
Neurosciences
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Axons
Nerve Regeneration
030104 developmental biology
nervous system
Calcium
Cellular
Nitric Oxide Synthase
030217 neurology & neurosurgery
Zdroj: Neuron
Neuron, Elsevier, 2019, 102 (2), pp.373-389.e6. ⟨10.1016/j.neuron.2019.01.050⟩
Neuron, 2019, 102 (2), pp.373-389.e6. ⟨10.1016/j.neuron.2019.01.050⟩
Neuron, vol 102, iss 2
ISSN: 0896-6273
Popis: 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-selectivecation 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 invivo accelerates regeneration, while its pharmacological activation invitro 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.
Databáze: OpenAIRE