The F-BAR protein NOSTRIN participates in FGF signal transduction and vascular development.
EMBO J
; 31(15): 3309-22, 2012 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-22751148
ABSTRACT
F-BAR proteins are multivalent adaptors that link plasma membrane and cytoskeleton and coordinate cellular processes such as membrane protrusion and migration. Yet, little is known about the function of F-BAR proteins in vivo. Here we report, that the F-BAR protein NOSTRIN is necessary for proper vascular development in zebrafish and postnatal retinal angiogenesis in mice. The loss of NOSTRIN impacts on the migration of endothelial tip cells and leads to a reduction of tip cell filopodia number and length. NOSTRIN forms a complex with the GTPase Rac1 and its exchange factor Sos1 and overexpression of NOSTRIN in cells induces Rac1 activation. Furthermore, NOSTRIN is required for fibroblast growth factor 2 dependent activation of Rac1 in primary endothelial cells and the angiogenic response to fibroblast growth factor 2 in the in vivo matrigel plug assay. We propose a novel regulatory circuit, in which NOSTRIN assembles a signalling complex containing FGFR1, Rac1 and Sos1 thereby facilitating the activation of Rac1 in endothelial cells during developmental angiogenesis.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vasos Sanguíneos
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Neovascularização Fisiológica
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
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Fatores de Crescimento de Fibroblastos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha