LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans

Leboutet, Romane; Largeau, Céline; Müller, Leonie; Prigent, Magali; Quinet, Grégoire; Rodríguez, Manuel Sánchez; Cuif, Marie-Hélène; Hoppe, Thorsten; Culetto, Emmanuel; Lefebvre, Christophe; Legouis, Renaud

doi:10.7554/elife.85748

Cited by 6 publications

(2 citation statements)

References 79 publications

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“…Finally, we checked whether autophagy was required for levamisole adaptation using the lgg-1(G116AG117 *) [44] mutant, which shows no developmental defect but has no autophagic activity. The blocking of autophagy did not prevent adaptation of lev-10(0) mutants (Table 1).…”

Section: Movement Recovery Is Associated With Increase In Autophagic ...mentioning

confidence: 99%

Calcineurin-Dependent Homeostatic Response of C. elegans Muscle Cells upon Prolonged Activation of Acetylcholine Receptors

Florin,

Bonneau,

Briseño-Roa

et al. 2023

Cells

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Pharmacological adaptation is a common phenomenon observed during prolonged drug exposure and often leads to drug resistance. Understanding the cellular events involved in adaptation could provide new strategies to circumvent this resistance issue. We used the nematode Caenorhabditis elegans to analyze the adaptation to levamisole, an ionotropic acetylcholine receptor agonist, used for decades to treat nematode parasitic infections. Genetic screens in C. elegans identified “adapting mutants” that initially paralyze upon exposure to levamisole as the wild type (WT), but recover locomotion after a few hours whereas WT remain paralyzed. Here, we show that levamisole induces a sustained increase in cytosolic calcium concentration in the muscle cells of adapting mutants, lasting several hours and preceding a decrease in levamisole-sensitive acetylcholine receptors (L-AChR) at the muscle plasma membrane. This decrease correlated with a drop in calcium concentration, a relaxation of the animal’s body and a resumption of locomotion. The decrease in calcium and L-AChR content depends on calcineurin activation in muscle cells. We also showed that levamisole adaptation triggers homeostatic mechanisms in muscle cells including mitochondria remodeling, lysosomal tubulation and an increase in autophagic activity. Levamisole adaptation thus provides a new experimental paradigm for studying how cells cope with calcium stress.

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Section: Movement Recovery Is Associated With Increase In Autophagic ...mentioning

confidence: 99%

Calcineurin-Dependent Homeostatic Response of C. elegans Muscle Cells upon Prolonged Activation of Acetylcholine Receptors

Florin,

Bonneau,

Briseño-Roa

et al. 2023

Cells

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“…The structural conservation of LGG-1/GABARAP and LGG-2/LC3 emphasizes their pivotal role in autophagy during developmental stages, longevity, and responses to stress (Meléndez et al, 2003) (Alberti et al, 2010) (Wu et al, 2015) (Chang et al, 2017). Recently, a lipidation-independent role of LGG-1 in autophagy was reported (Leboutet et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy

Jha,

Pispa,

Holmberg

2024

Preprint

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The autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are the two major intracellular proteolytic systems that mediate protein turnover in eukaryotes. Although a crosstalk exists between these two systems, it is still unclear how UPS and ALP interact in vivo. Here, we have investigated how impaired function of the proteasome-associated deubiquitinating enzyme (DUB) Uchl5/UBH-4, a regulator of proteasome activity, affects autophagy in human cells and in various tissues in a multicellular organism. We have used the established GFP-LC3-RFP-LC3ΔG autophagy reporter HeLa cell line and show that downregulation of Uchl5 by siRNA reduces autophagy, which is similar to a previously reported role of the proteasome-associated DUB Usp14 on autophagy. Exposing Caenorhabditis elegans carrying the autophagy reporter mCherry::GFP::LGG-1 to ubh-4 or usp-14 RNAi, or to their pharmacological inhibitors, results in diverse effects regarding the numbers of autophagosomes and autolysosomes in the intestine, hypodermal seam cells and the pharynx. Our results reveal that the proteasome-associated DUBs Uchl5/UBH-4 and Usp14 affect autophagy in a differential tissue manner. A deeper insight into the interplay between UPS and ALP in various tissues in vivo has the potential to promote development of therapeutic approaches for disorders associated with proteostasis dysfunction.

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Egg multivesicular bodies elicit an LC3-associated phagocytosis-like pathway to degrade paternal mitochondria after fertilization

Ben-Hur,

Sernik,

Afar

et al. 2024

Nat Commun

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Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination after fertilization are far less clear. Using Drosophila, we show that special egg-derived multivesicular body vesicles promote paternal mitochondrial elimination by activating an LC3-associated phagocytosis-like pathway, a cellular defense pathway commonly employed against invading microbes. Upon fertilization, these egg-derived vesicles form extended vesicular sheaths around the sperm flagellum, promoting degradation of the sperm mitochondrial derivative and plasma membrane. LC3-associated phagocytosis cascade of events, including recruitment of a Rubicon-based class III PI(3)K complex to the flagellum vesicular sheaths, its activation, and consequent recruitment of Atg8/LC3, are all required for paternal mitochondrial elimination. Finally, lysosomes fuse with strings of large vesicles derived from the flagellum vesicular sheaths and contain degrading fragments of the paternal mitochondrial derivative. Given reports showing that in some mammals, the paternal mitochondria are also decorated with Atg8/LC3 and surrounded by multivesicular bodies upon fertilization, our findings suggest that a similar pathway also mediates paternal mitochondrial elimination in other flagellated sperm-producing organisms.

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LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans

Cited by 6 publications

References 79 publications

Calcineurin-Dependent Homeostatic Response of C. elegans Muscle Cells upon Prolonged Activation of Acetylcholine Receptors

Calcineurin-Dependent Homeostatic Response of C. elegans Muscle Cells upon Prolonged Activation of Acetylcholine Receptors

Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy

Egg multivesicular bodies elicit an LC3-associated phagocytosis-like pathway to degrade paternal mitochondria after fertilization

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