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  • The F-BAR protein NOSTRIN participates in FGF signal transduction and vascular development

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    Author(s)
    Kovacevic, Igor
    Hu, Jiong
    Siehoff-Icking, Ann
    Opitz, Nils
    Griffin, Aliesha
    Perkins, Andrew C
    Munn, Alan L
    Mueller-Esterl, Werner
    Popp, Ruediger
    Fleming, Ingrid
    Jungblut, Benno
    Hoffmeister, Meike
    Oess, Stefanie
    Griffith University Author(s)
    Munn, Alan L.
    Year published
    2012
    Metadata
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    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 ...
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    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.
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    Journal Title
    The EMBO Journal
    Volume
    31
    Issue
    15
    DOI
    https://doi.org/10.1038/emboj.2012.176
    Copyright Statement
    © 2012 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
    Subject
    Biological sciences
    Signal transduction
    Animal physiology - cell
    Animal cell and molecular biology
    Information and computing sciences
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/49812
    Collection
    • Journal articles

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