Home > Publications Database > RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury. > print

001     162729
005     20230915092403.0
024 7 _ |a 10.1016/j.neuron.2021.08.014
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024 7 _ |a 0896-6273
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024 7 _ |a 1097-4199
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037 _ _ |a DZNE-2021-01386
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100 1 _ |a Stern, Sina
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245 _ _ |a RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury.
260 _ _ |a New York, NY
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520 _ _ |a 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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650 _ 7 |a F-actin density
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650 _ 7 |a RhoA
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650 _ 7 |a YAP signaling
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650 _ 7 |a astrocyte reactivity
|2 Other
650 _ 7 |a axon regeneration
|2 Other
650 _ 7 |a microtubule protrusion
|2 Other
650 _ 7 |a myosin II
|2 Other
650 _ 2 |a Actins: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Astrocytes: metabolism
|2 MeSH
650 _ 2 |a Axons: metabolism
|2 MeSH
650 _ 2 |a Central Nervous System: metabolism
|2 MeSH
650 _ 2 |a Central Nervous System: pathology
|2 MeSH
650 _ 2 |a Central Nervous System Diseases: metabolism
|2 MeSH
650 _ 2 |a Central Nervous System Diseases: pathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Nerve Regeneration: physiology
|2 MeSH
650 _ 2 |a rhoA GTP-Binding Protein: metabolism
|2 MeSH
700 1 _ |a Hilton, Brett Jason
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700 1 _ |a Burnside, Emily
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700 1 _ |a Dupraz, Sebastian
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700 1 _ |a Handley, Emily
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700 1 _ |a Gonyer, Jessica
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700 1 _ |a Brakebusch, Cord
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700 1 _ |a Bradke, Frank
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773 _ _ |a 10.1016/j.neuron.2021.08.014
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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