Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

Détails

Ressource 1Télécharger: Maldonado2017.pdf (5781.10 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_0A3288975691
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.
Périodique
Biochimica et Biophysica Acta. Molecular Cell Research
Auteur(s)
Maldonado H., Calderon C., Burgos-Bravo F., Kobler O., Zuschratter W., Ramirez O., Härtel S., Schneider P., Quest A.F., Herrera-Molina R., Leyton L.
ISSN
0167-4889
ISSN-L
1879-2596
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
1864
Numéro
2
Pages
243-254
Langue
anglais
Résumé
Two key proteins for cellular communication between astrocytes and neurons are αvβ3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvβ3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvβ3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the β3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvβ3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication.

Mots-clé
alpha v beta 3 integrin, RhoA, STED microscopy, GPI-anchored proteins, Interaction in trans, Cell adhesion molecules
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/12/2016 19:20
Dernière modification de la notice
08/05/2019 14:11
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