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RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury.
Stern, Sina; Hilton, Brett J; Burnside, Emily R; Dupraz, Sebastian; Handley, Emily E; Gonyer, Jessica M; Brakebusch, Cord; Bradke, Frank.
Affiliation
  • Stern S; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.
  • Hilton BJ; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.
  • Burnside ER; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.
  • Dupraz S; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.
  • Handley EE; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.
  • Gonyer JM; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.
  • Brakebusch C; Biotech Research and Innovation Centre, Biomedical Institute, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
  • Bradke F; Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany. Electronic address: frank.bradke@dzne.de.
Neuron ; 109(21): 3436-3455.e9, 2021 11 03.
Article in En | MEDLINE | ID: mdl-34508667
ABSTRACT
An inhibitory extracellular milieu and neuron-intrinsic processes prevent axons from regenerating in the adult central nervous system (CNS). Here we show how the two aspects are interwoven. Genetic loss-of-function experiments determine that the small GTPase RhoA relays extracellular inhibitory signals to the cytoskeleton by adapting mechanisms set in place during neuronal polarization. In response to extracellular inhibitors, neuronal RhoA restricts axon regeneration by activating myosin II to compact actin and, thereby, restrain microtubule protrusion. However, astrocytic RhoA restricts injury-induced astrogliosis through myosin II independent of microtubules by activating Yes-activated protein (YAP) signaling. Cell-type-specific deletion in spinal-cord-injured mice shows that neuronal RhoA activation prevents axon regeneration, whereas astrocytic RhoA is beneficial for regenerating axons. These data demonstrate how extracellular inhibitors regulate axon regeneration, shed light on the capacity of reactive astrocytes to be growth inhibitory after CNS injury, and reveal cell-specific RhoA targeting as a promising therapeutic avenue.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Axons / Central Nervous System Diseases / Actins / RhoA GTP-Binding Protein / Nerve Regeneration Limits: Animals Language: En Journal: Neuron Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Axons / Central Nervous System Diseases / Actins / RhoA GTP-Binding Protein / Nerve Regeneration Limits: Animals Language: En Journal: Neuron Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: