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Rôle des récepteurs autophagiques dans la maturation des autophagosomes

Pauline Verlhac 1 
1 APY - Autophagie infection et immunité - Autophagy Infection Immunity
CIRI - Centre International de Recherche en Infectiologie - UMR
Abstract : Xenophagy relies on the ability of the autophagy process to selectively entrap intracellular pathogens within autophagosomes to degrade them into autolysosomes. The selectivity of the process relies on proteins named autophagy receptors that share the ability to recognise cytosolic cargos on one hand and autophagosome-bound members of the ATG8 family on the other. Among autophagy receptors NDP52 has been described to target Salmonella Typhimurium to the growing autophagosome. We describe a new unexpected role for NDP52, as this receptor also regulates the maturation of Salmonella-containing autophagosomes and during ongoing autophagy. Interestingly, the role of NDP52 in maturation is independent from its role in targeting as they rely on different binding domains and protein partners. We also show that other autophagy receptors also mediate autophagosome maturation such as Optineurin. Therefore, our work shows that NDP52 plays a dual function during xenophagy first by targeting bacteria to growing autophagosomes and then by assuring autophagosome maturation. Moreover, we also provide insights as to how these dual roles are regulated by post-translational modifications of autophagy receptors.This work demonstrates that autophagy receptors have other roles beyond pathogen targeting that are also crucial for an efficient xenophagy. Moreover, autophagy receptors are also necessary for autophagy completion in uninfected cells. These results strengthen our understanding of both ongoing autophagy and xenophagy molecular mechanisms
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  • HAL Id : tel-01540361, version 1

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Pauline Verlhac. Rôle des récepteurs autophagiques dans la maturation des autophagosomes. Biologie cellulaire. Université de Lyon, 2016. Français. ⟨NNT : 2016LYSE1138⟩. ⟨tel-01540361⟩

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