CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines.: CHMP2B and dendritic spines

Abstract : The highly conserved ESCRT-III complex is responsible for deformation and cleavage of membranes during endosomal trafficking and other cellular activities. In humans, dominant mutations in the ESCRT-III subunit CHMP2B cause frontotemporal dementia (FTD). The decade-long process leading to this cortical degeneration is not well understood. One possibility is that, akin to other neurodegenerative diseases, the pathogenic protein affects the integrity of dendritic spines and synapses before any neuronal death. Using confocal microscopy and 3D reconstruction, we examined whether expressing the FTD-linked mutants CHMP2B(intron5) and CHMP2B(Delta10) in cultured hippocampal neurons modified the number or structure of spines. Both mutants induced a significant decrease in the proportion of large spines with mushroom morphology, without overt degeneration. Furthermore, CHMP2B(Delta10) induced a drop in frequency and amplitude of spontaneous excitatory postsynaptic currents, suggesting that the more potent synapses were lost. These effects seemed unrelated to changes in autophagy. Depletion of endogenous CHMP2B by RNAi resulted in morphological changes similar to those induced by mutant CHMP2B, consistent with dominant-negative activity of pathogenic mutants. Thus, CHMP2B is required for spine growth. Taken together, these results demonstrate that a mutant ESCRT-III subunit linked to a human neurodegenerative disease can disrupt the normal pattern of spine development.
Type de document :
Article dans une revue
Journal of Cell Science, Company of Biologists, 2010, 123 (Pt 17), pp.2943-54. 〈10.1242/jcs.068817〉
Liste complète des métadonnées

Littérature citée [36 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00538917
Contributeur : Sandrine Fraboulet <>
Soumis le : mardi 23 novembre 2010 - 15:04:04
Dernière modification le : jeudi 28 juin 2018 - 09:52:01
Document(s) archivé(s) le : jeudi 24 février 2011 - 03:17:20

Fichiers

inserm-00538917_edited.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Agnès Belly, Gilles Bodon, Béatrice Blot, Alexandre Bouron, Rémy Sadoul, et al.. CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines.: CHMP2B and dendritic spines. Journal of Cell Science, Company of Biologists, 2010, 123 (Pt 17), pp.2943-54. 〈10.1242/jcs.068817〉. 〈inserm-00538917〉

Partager

Métriques

Consultations de la notice

272

Téléchargements de fichiers

457