WIP modulates dendritic spine actin cytoskeleton by transcriptional control of lipid metabolic enzymes
- Ana Franco-Villanueva1,2,†,
- Estefanía Fernández-López1,2,†,
- Enrique Gabandé-Rodríguez1,
- Inmaculada Bañón-Rodríguez2,
- Jose Antonio Esteban1,
- Inés M. Antón2,* and
- María Dolores Ledesma1,*
+Author Affiliations
- ↵*To whom correspondence should be addressed at: Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Madrid 28049, Spain. Tel: +34 915855312; Fax: +34 915854506; Email:ianton@cnb.csic.es (I.M.A.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Nicolás Cabrera 1, Madrid 28049, Spain. Tel: +34 911964535; Fax +34 919164420; Email:dledesma@cbm.csic.es (M.D.L.)
- Received January 27, 2014.
- Revision received March 28, 2014.
- Accepted March 31, 2014.
Abstract
We identify Wiskott–Aldrich syndrome protein (WASP)-interacting protein (WIP) as a novel component of neuronal synapses whose absence increases dendritic spine size and filamentous actin levels in an N-WASP/Arp2/3-independent, RhoA/ROCK/profilinIIa-dependent manner. These effects depend on the reduction of membrane sphingomyelin (SM) due to transcriptional upregulation of neutral sphingomyelinase (NSM) through active RhoA; this enhances RhoA binding to the membrane, raft partitioning and activation in steady state but prevents RhoA changes in response to stimulus. Inhibition of NSM or SM addition reverses RhoA, filamentous actin and functional anomalies in synapses lacking WIP. Our findings characterize WIP as a link between membrane lipid composition and actin cytoskeleton at dendritic spines. They also contribute to explain cognitive deficits shared by individuals bearing mutations in the region assigned to the gene encoding for WIP.
- © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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