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Culetto, E.

Publications and source records attributed to Culetto, E..

2 recordsLinked to original sources

Reticulon dependent ER-phagy mediates adaptation to heat stress in Caenorhabditis elegans

The selective degradation of ER by autophagy, named ER-phagy, promotes the recovery of ER homeostasis after a stress. Depending on the ER stress, different types of ER-phagy involve various selective autophagy receptors. In this study, we report a macroER-phagy induced by the fragmentation of tubular ER in response to acute heat stress. We identified a novel ER-phagy receptor encoded by the reticulon long isoform RET-1d. RET-1d is mainly expressed in the nervous system and the epidermis and colocalize with the ubiquitin-like autophagy protein LGG-1/GABARAP during heat stress induced autophagy. Two LIR motifs in the long intrinsically disordered region of RET-1d mediate its interaction with LGG-1 protein. The specific depletion of RET-1d isoform resulted in a delay in autophagosome biogenesis and a decrease in the capacity of animals to adapt to heat stress. Our data revealed a RET-1d dependent ER-phagy mechanism that takes place in neurons and epidermis and participates to the adaptation of C. elegans to heat stress.

cell biology↗

LGG-1/GABARAP lipidation is dispensable for autophagy and development in C .elegans

The ubiquitin-like proteins Atg8/LC3/GABARAP are required for multiple steps of autophagy such as initiation, cargo recognition and engulfment, vesicle closure and degradation. Most of LC3/GABARAP functions are considered dependent on their post-translational modifications and addressing to membranes through a conjugation to a lipid, the phosphatidylethanolamine. Contrarily to mammals, C. elegans possesses single homologs of LC3 and GABARAP families, named LGG-2 and LGG-1. Using site directed mutagenesis, we inhibited the conjugation of LGG-1 to the autophagosomal membrane and generated mutants that express only cytosolic forms, either the precursor or the cleaved protein. LGG-1 is an essential gene for autophagy and development in C. elegans, but we discovered that its functions could be fully achieved independently of its localization to the membrane. This study reveals an essential role for the cleaved form of LGG-1 in autophagy but also in an autophagy independent embryonic function. Our data question the use of the lipidated GABARAP/LC3 as the main marker of autophagic flux and highlight the high plasticity of autophagy.

cell biology↗