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The F‐BAR protein NOSTRIN participates in FGF signal transduction and vascular development
Author(s) -
Kovacevic Igor,
Hu Jiong,
SiehoffIcking Ann,
Opitz Nils,
Griffin Aliesha,
Perkins Andrew C,
Munn Alan L,
MüllerEsterl Werner,
Popp Rüdiger,
Fleming Ingrid,
Jungblut Benno,
Hoffmeister Meike,
Oess Stefanie
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.176
Subject(s) - griffin , library science , medical school , art history , classics , medicine , history , computer science , medical education
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.