RT Journal Article
SR Electronic
T1 Regulation of Postsynaptic Function by the Dementia-Related ESCRT-III Subunit CHMP2B
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3155
OP 3173
DO 10.1523/JNEUROSCI.0586-14.2015
VO 35
IS 7
A1 Chassefeyre, Romain
A1 Martínez-Hernández, José
A1 Bertaso, Federica
A1 Bouquier, Nathalie
A1 Blot, Béatrice
A1 Laporte, Marine
A1 Fraboulet, Sandrine
A1 Couté, Yohann
A1 Devoy, Anny
A1 Isaacs, Adrian M.
A1 Pernet-Gallay, Karin
A1 Sadoul, Rémy
A1 Fagni, Laurent
A1 Goldberg, Yves
YR 2015
UL http://www.jneurosci.org/content/35/7/3155.abstract
AB The charged multivesicular body proteins (Chmp1–7) are an evolutionarily conserved family of cytosolic proteins that transiently assembles into helical polymers that change the curvature of cellular membrane domains. Mutations in human CHMP2B cause frontotemporal dementia, suggesting that this protein may normally control some neuron-specific process. Here, we examined the function, localization, and interactions of neuronal Chmp2b. The protein was highly expressed in mouse brain and could be readily detected in neuronal dendrites and spines. Depletion of endogenous Chmp2b reduced dendritic branching of cultured hippocampal neurons, decreased excitatory synapse density in vitro and in vivo, and abolished activity-induced spine enlargement and synaptic potentiation. To understand the synaptic effects of Chmp2b, we determined its ultrastructural distribution by quantitative immuno-electron microscopy and its biochemical interactions by coimmunoprecipitation and mass spectrometry. In the hippocampus in situ, a subset of neuronal Chmp2b was shown to concentrate beneath the perisynaptic membrane of dendritic spines. In synaptoneurosome lysates, Chmp2b was stably bound to a large complex containing other members of the Chmp family, as well as postsynaptic scaffolds. The supramolecular Chmp assembly detected here corresponds to a stable form of the endosomal sorting complex required for transport-III (ESCRT-III), a ubiquitous cytoplasmic protein complex known to play a central role in remodeling of lipid membranes. We conclude that Chmp2b-containing ESCRT-III complexes are also present at dendritic spines, where they regulate synaptic plasticity. We propose that synaptic ESCRT-III filaments may function as a novel element of the submembrane cytoskeleton of spines.