Journal Article

DZNE-2021-01386

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury.

Stern, S. (First author)DZNE* ; Hilton, B. J.DZNE* ; Burnside, E.DZNE* ; Dupraz, S.DZNE* ; Handley, E.DZNE* ; Gonyer, J.DZNE* ; Brakebusch, C. ; Bradke, F. (Last author)DZNE*

2021
Elsevier New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.neuron.2021.08.014

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.

Keyword(s): Actins: metabolism (MeSH) ; Animals (MeSH) ; Astrocytes: metabolism (MeSH) ; Axons: metabolism (MeSH) ; Central Nervous System: metabolism (MeSH) ; Central Nervous System: pathology (MeSH) ; Central Nervous System Diseases: metabolism (MeSH) ; Central Nervous System Diseases: pathology (MeSH) ; Mice (MeSH) ; Nerve Regeneration: physiology (MeSH) ; rhoA GTP-Binding Protein: metabolism (MeSH) ; F-actin density ; RhoA ; YAP signaling ; astrocyte reactivity ; axon regeneration ; microtubule protrusion ; myosin II

---

Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---