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Janus

Deciphering the autophagy related and unrelated functions of Atg8 repertoire in C. elegans
Funder: French National Research Agency (ANR)Project code: ANR-23-CE13-0013
Funder Contribution: 529,538 EUR
Description

The Atg8/LC3/GABARAP family of ubiquitin-like proteins is a main player of the macroautophagy pathway, a stress-resistance process that maintains cellular homeostasis by promoting the degradation of cytoplasmic components and organelles within lysosomes. Atg8s are addressed to double membrane vesicles termed autophagosomes (AP), participating to the initiation, cargo recognition/engulfment, and vesicle closure. In addition, Atg8s also function in autophagy unrelated pathways, either conjugated to single-membrane vesicles (CASM) or independently of membrane anchorage. However, the molecular mechanisms and the regulations underlying the multiple roles of Atg8s are not well understood. The Janus consortium federate partners working on Autophagy, Proteostasis and Stress, and complementary expertise on cellular biology, genetics, proteomics and big data analyses. The Janus project explores the two faces of LC3/GABARAP functions within the cell and aims to characterize the molecular mechanisms allowing "spatio-temporal functionality" in autophagy-related and unrelated processes. Janus will describe and quantify the variability and versatility of LC3/GABARAP functions. It takes advantage of C. elegans for in vivo studies of several autophagy processes, but also CASM processes and developmental functions. This tiny animal with multiple tissues but with only two LC3/GABARAP proteins (six in humans) will foster the exploration of their specific roles and the elaboration of a functional model for LC3/GABARAP repertoire. The novelty and ambition of Janus is to obtain a detailed and comprehensive view of Atg8s functions and to better understand how they participate to stress sensing and homeostasis through autophagy-related and unrelated processes.

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