WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory.
J Neurosci
; 31(7): 2447-60, 2011 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-21325512
ABSTRACT
The WAVE-associated Rac GAP, WRP, is thought to regulate key aspects of synapse development and function and may be linked to mental retardation in humans. WRP contains a newly described inverse F-BAR (IF-BAR) domain of unknown function. Our studies show that this domain senses/facilitates outward protrusions analogous to filopodia and that the molecular basis for this is likely explained by a convex lipid-binding surface on the WRP IF-BAR domain. In dendrites the IF-BAR domain of WRP forms a bud on the shaft from which precursors to spines emerge. Loss of WRP in vivo and in vitro results in reduced density of spines. In vivo this is primarily a loss of mushroom-shaped spines. Developmentally, WRP function is critical at the onset of spinogenesis, when dendritic filopodia are prevalent. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated. Results from these studies confirm that loss of WRP is linked to impaired learning and memory.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Ativadoras de GTPase
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Espinhas Dendríticas
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Domínios e Motivos de Interação entre Proteínas
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Transtornos da Memória
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos