The RhoGEF DOCK10 is essential for dendritic spine morphogenesis.
Fiche publication
Date publication
avril 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GASMAN Stéphane
Tous les auteurs :
Jaudon F, Raynaud F, Wehrle R, Bellanger JM, Doulazmi M, Vodjdani G, Gasman S, Fagni L, Dusart I, Debant A, Schmidt S
Lien Pubmed
Résumé
By regulating actin cytoskeleton dynamics, Rho GTPases and their activators RhoGEFs are implicated in various aspects of neuronal differentiation, including dendritogenesis and synaptogenesis. Purkinje cells (PCs) of the cerebellum, by developing spectacular dendrites covered with spines, represent an attractive model system in which to decipher the molecular signaling underlying these processes. To identify novel regulators of dendritic spine morphogenesis among members of the poorly characterised DOCK family of RhoGEFs, we performed a gene expression profiling of FACS-purified murine PCs, at various stages of their postnatal differentiation. We found a strong increase in the expression of the Cdc42-specific GEF DOCK10. Depleting DOCK10 in organotypic cerebellar cultures resulted in dramatic dendritic spine defects in PCs. Accordingly, in mouse hippocampal neurons, depletion of DOCK10 or expression of a DOCK10 GEF-dead mutant led to a strong decrease in spine density and size. Conversely, overexpression of DOCK10 led to increased spine formation. We show that DOCK10 function in spinogenesis was mediated mainly by Cdc42 and its downstream effectors N-WASP and PAK3, although we found that DOCK10 was also able to activate Rac1. Our global approach thus identified an unprecedented function for DOCK10 as a novel regulator of dendritic spine morphogenesis, via a Cdc42-mediated pathway.
Référence
Mol Biol Cell. 2015 Apr 7. pii: mbc.E14-08-1310.