RTG-ReMPro
Projects
P8 Panáková
Elucidating the Prickle-dependent and independent protein-protein
interactions of the membrane protein Vangl2 in myoblasts and in
developing heart muscle cells
Objectives
Our goal is to identify how the posttranslational modifications of Vangl2 and Prickle affect the composition of Vangl2 protein complexes specifically in heart muscle cells. We aim at elucidating the cardiac-specific transducers of the PCP activity to decipher different cardiac disease states that occur when PCP signaling is disrupted. We hypothesize that the presence or absence of Prickle (or its lack of prenylation) enables Vangl2 to scaffold different reversible protein complexes that may lead to recruitment of different downstream effectors. We will elucidate the Vangl2 protein interactome in cells as well as in in vivo in zebrafish.
Aim i) Identification and characterization of the Vangl2 protein interactome in myoblasts and zebrafish embryos
Aim ii) Characterization of the Vangl2 protein interactions in cells and developing zebrafish heart
PCP in the heart. Top; graphic of PCP core proteins in the developing epithelium of the zebrafish heart with potential effector proteins in grey. Bottom; the Vangl2-Prickle complexes will be analysed by Proximity Ligation Assays (Vangl2 tagged with TurboID in red) followed by Mass Spec in Prickle-dependent manner (1) and functionally tested (2) in cells (left) and zebrafish (right) using actomyosin abundance, localization and activity as a primary read-out.
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