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Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée

Abstract : The discovery of the involvement of lipids in membrane trafficking is one of the major recent progress in cell biology. My thesis work focused on phosphatidic acid (PA), the simplest phospholipid. PA synthesis by phospholipase D (PLD) plays a crucial role during phagocytosis and regulated exocytosis, but its precise dynamics, as well as the mode of action of the different PA species, remain unknown. I characterized three PA binding domains allowing a better understanding of the interaction between proteins and PA and leading to the generation of genetic sensors for PA in cells. Thus I could visualize PA synthesis during phagocytosis and identified that the small GTPase Arf6 regulates PLD activity and consequently PA synthesis. My work also reveals that PLD modulates several steps during exocytosis in neuroendocrine cells. Further lipidomics and rescue experiments allowed me to show that mono- and polyunsaturated forms of PA are involved in distinct steps of exocytosis.
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Emeline Tanguy. Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée. Biologie moléculaire. Université de Strasbourg, 2019. Français. ⟨NNT : 2019STRAJ112⟩. ⟨tel-02919857⟩

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