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Mécanismes de tri et voies de transport intracellulaire des protéines de la membrane du lysosome

Abstract : More than sixty different proteins are inserted into the membrane of the lysosome, participating in the various functions of this organelle. But the intracellular trafficking pathways that lead lysosomal membrane proteins (LMPs) to this organelle are not well understood. Interestingly, some LMPs exhibit abnormal intracellular localisations in some cancers. This is the case of the glycoprotein LAMP1 which is overexpressed at the cell surface in several cancers, from where it plays several roles in tumour aggressiveness. Thanks to the Retention Using Selective Hooks (RUSH) system, allowing the synchronisation of the transport along the secretory pathway, we have shown that neosynthesized LAMP1 reaches the plasma membrane before entering endosomes. Comparing the routes followed by different LMPs also revealed that LAMP1 and LIMP2 are sorted at the Golgi apparatus, LIMP2 being concentrated in characteristic vesicular and clathrin-free structures. We have also shown that, surprisingly, this sorting at the level of the Golgi apparatus is independent of clathrin adapters recruitment signals carried in the C-terminal tails of these two LMPs. To investigate what mechanisms might be involved in the overexposure of LAMP1 at the cell surface of certain cancers, we also performed a gene knock-out screen based on CRISPR-Cas9 technology. We selected genes whose inactivation affected LAMP1 levels at the surface and obtained many candidate genes that are under study.
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https://tel.archives-ouvertes.fr/tel-03141343
Contributor : Abes Star :  Contact
Submitted on : Monday, February 15, 2021 - 11:18:53 AM
Last modification on : Wednesday, February 17, 2021 - 3:30:58 AM

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  • HAL Id : tel-03141343, version 1

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Jason Ecard. Mécanismes de tri et voies de transport intracellulaire des protéines de la membrane du lysosome. Biologie cellulaire. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS094⟩. ⟨tel-03141343⟩

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