Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma.
Axon regeneration
Focal adhesion kinase
Integrin
Rab GTPase
Rabphilin3
Spinal cord injury
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
20
01
2022
revised:
09
03
2022
accepted:
04
04
2022
pubmed:
11
4
2022
medline:
4
5
2022
entrez:
10
4
2022
Statut:
ppublish
Résumé
Neural repair after traumatic spinal cord injury depends upon the restoration of neural networks via axonal sprouting and regeneration. Our previous genome wide loss-of-function screen identified Rab GTPases as playing a prominent role in preventing successful axon sprouting and regeneration. Here, we searched for Rab27b interactors and identified Rabphilin3A as an effector within regenerating axons. Growth cone Rabphilin3a colocalized and physically associated with integrins at puncta in the proximal body of the axonal growth cone. In regenerating axons, loss of Rabphilin3a increased integrin enrichment in the growth cone periphery, enhanced focal adhesion kinase activation, increased F-actin-rich filopodial density and stimulated axon extension. Compared to wild type, mice lacking Rabphilin3a exhibited greater regeneration of retinal ganglion cell axons after optic nerve crush as well as greater corticospinal axon regeneration after complete thoracic spinal cord crush injury. After moderate spinal cord contusion injury, there was greater corticospinal regrowth in the absence of Rph3a. Thus, an endogenous Rab27b - Raphilin3a pathway limits integrin action in the growth cone, and deletion of this monomeric GTPase pathway permits reparative axon growth in the injured adult mammalian central nervous system.
Identifiants
pubmed: 35398339
pii: S0014-4886(22)00095-4
doi: 10.1016/j.expneurol.2022.114070
pmc: PMC9555232
mid: NIHMS1838967
pii:
doi:
Substances chimiques
Integrins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
114070Subventions
Organisme : NEI NIH HHS
ID : P30 EY026878
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097283
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
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