WIP modulates dendritic spine actin cytoskeleton by transcriptional control of lipid metabolic enzymes. (3rd April 2014)

• Record Type: Journal Article
• Authors: Franco-Villanueva, Ana; Fernández-López, Estefanía; Gabandé-Rodríguez, Enrique; Bañón-Rodríguez, Inmaculada; Esteban, Jose Antonio; Antón, Inés M.; Ledesma, María Dolores
• Is Part Of: Human molecular genetics. Volume 23:Number 16(2014:Aug. 15)
• Page Start: 4383
• Page End: 4395
• Publication Date: 2014-04-03
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddu155
• Languages: English
• ISSNs: 0964-6906

Abstract

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.