Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking.
Actin-Related Protein 2-3 Complex
Actins
/ metabolism
Animals
Astrocytes
/ metabolism
Brain
/ metabolism
Brain Injuries
/ metabolism
Brain Injuries, Traumatic
/ metabolism
Cell Movement
Central Nervous System
/ metabolism
Cicatrix
/ metabolism
Disease Models, Animal
Gliosis
/ metabolism
Mice
Mice, Knockout
Neuropeptides
/ genetics
Neuroprotection
Transcriptome
rab GTP-Binding Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 03 2021
05 03 2021
Historique:
received:
10
07
2020
accepted:
27
01
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
20
3
2021
Statut:
epublish
Résumé
The brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. In turn, DBN loss leads to defective astrocyte scar formation and excessive neurodegeneration following brain injuries. At the cellular level, we show that DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds, facilitating the formation of RAB8-positive membrane tubules. This injury-specific RAB8 membrane compartment serves as hub for the trafficking of surface proteins involved in astrogliosis and adhesion mediators, such as β1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice.
Identifiants
pubmed: 33674568
doi: 10.1038/s41467-021-21662-x
pii: 10.1038/s41467-021-21662-x
pmc: PMC7935889
doi:
Substances chimiques
Actin-Related Protein 2-3 Complex
0
Actins
0
Neuropeptides
0
Rab8 protein, mouse
0
drebrins
0
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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