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Glypican5-supported endocytic control of BMP4 signaling

Objectif

Increasingly, the glypicans, major membrane proteins that supply heparan sulfate at the surface of cells, emerge as essential for the reception and dissemination of morphogenetic signals. While the best recognized role of endocytosis in signaling is to down-regulate the signal by sending the receptor and/or the ligand to degradative compartments such as lysosomes, it has now become clear that endocytosis also contributes to activation of signalling. In this project, we propose to explore the importance of glypicans for mechanisms of endocytic/exocytic trafficking and fine-tuning of signalling. We suspect that, by associating with specific protein sorting and trafficking machineries, glypicans control the formation of distinctive ‘signalling endosomes’, involved in the transcytosis of HS-cargo and its recycling to the cell surface, influencing what signal-transduction machineries are activated, where they are activated, and for how long. This working hypothesis is explored, concentrating on the effect of Glypican-5 on Bmp-4 signaling, in vitro, by cellular and biochemical assays, tracing glypican and glypican-interacting proteins, and by functional interference, using siRNA, and in vivo, in zebra fish embryos, using the injection of anti-sense morpholinos and mRNAs. Using these combined and integrated approaches in test tubes, cells and model organisms, we expect identifying novel mechanisms of vesicular trafficking that are important for development, developmental disorders, and acquired disease. In general, this project proposed will support the career development of the researcher by enhancing her competence diversification through a complete training. This fellowship is an opportunity for the applicant to attain a leading independent position.

Appel à propositions

FP7-PEOPLE-2009-IEF
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Coordinateur

VIB VZW
Contribution de l’UE
€ 159 100,00
Adresse
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgique

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Région
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Type d’activité
Research Organisations
Contact administratif
Rik Audenaert (Mr.)
Liens
Coût total
Aucune donnée