CGM - Department Cellular Dynamics and Development
Autophagy and development
Team leader: Renaud LEGOUIS
Last update: 28-Nov-2011
The team
Emmanuel Culetto, Associate professor, Paris-Sud 11
Céline Jenzer, Master2 Student, Paris-Sud 11
Christophe Lefebvre, Associate professor, Paris-Sud 11
Renaud Legouis, PI, Directeur de Recherche, Inserm
Marion Segalen, Postdoctoral fellow
Address and phone number
CNRS-CGM
Avenue de la Terrasse - Bât. 26
91198 GIF-SUR-YVETTE
FRANCE
Phone : 33 (0)1 69 82 43 74
Telecopy : 33(0)1 69 82 43 86
Topics
Recent studies have highlighted the large variety of physiological and pathophysiological roles of autophagy such as developmental process, cell death, anti-aging, antigen presentation, elimination of microorganisms and tumour suppression. Autophagy is mainly studied in yeast or in cell culture and there are only few models which allow to investigate its role by in vivo and in toto experimental approaches.
Caenorhabditis elegans offers the possibility to analyze the autophagic process in several different physiological conditions: development, stress and senescence. Numerous reports describe the presence of increase levels of autophagy for various diseases, however its role could be sometimes protective sometimes deleterious. For these reasons, it is essential to generate models to analyze autophagy on a whole organism both in physiological and pathological conditions.
We contributed to demonstrate that Caenorhabditis elegans is a good model to analyze the autophagic process in several different developmental processes and we have characterized the relationships between autophagosomes and endosomes. Because the autophagic pathway is highly conserved in metazoans, data obtained in C. elegans could be essential to understand the role of autophagy in humans. By using in vivo/in toto genetic approaches in a model animal, our objective is to better understand the roles of autophagy during development, differentiation and disease.
Our recent results can be summarized in four points:
- there is a common compartment between endosomes and autophagosomes in C. elegans,
- autophagy has a protective role on endosomal dysfunctions,
- inactivation of autophagosomal proteins LGG-1 and LGG-2 synergistically affects the development and longevity.
- autophagy specifically degrades paternal mitochondria after fertilization (allophagy).
By using in vivo/in toto genetic approaches in a model animal, our objective is to better understand the roles of autophagy during development, differentiation and disease. Our recent experiments revealed that autophagy is essential for multiple developmental and physiological processes in C. elegans a model system offering a large panel of techniques and in particular genetics, biochemistry, and cell biology.
Links
Le Club français de l’autophagie (French Club about Autophagy) ;
Selection of publications
Djeddi, A., Michelet, X., Culetto, E., Alberti, A., Barois, N. and Legouis, R. (2012) Induction of autophagy in ESCRT mutant is an adaptive response for cell survival in C. elegans. J Cell Sci, 125(3) :68-94
Al Rawi S, Louvet-Vallée S, Djeddi A, Sachse M, Culetto E, Hajjar C, Boyd L, Legouis R*, Galy V.* (2012). Allophagy: a macroautophagic process degrading spermatozoid-inherited organelles. Autophagy, 8(3). *equal contribution
Al Rawi, S., Louvet-Vallée, S., Djeddi, A., Sachse, M., Culetto, E., Hajjar, C., Boyd, L., Legouis, R.* and Galy, V.* (2011) Postfertilization Autophagy of Sperm Organelles Prevents Paternal Mitochondrial DNA Transmission.Science, 334 (6059) 1144-1147. *equal contribution
Alberti, A.*, Michelet, X.*, Djeddi, A.*, Legouis, R. (2010) The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. Autophagy, 6 (5) 622-633. *equal contribution.
Michelet, X., Djeddi, A. and Legouis, R. (2010) Developmental and cellular functions of ESCRT machinery in pluricellular organisms. Biol Cell, 102 (3) 191-202. Review.
Michelet, X., Alberti, A., Benkemoun, L., Roudier, N., Lefebvre, C. and Legouis, R. (2009) The ESCRT-III protein CeVPS-32 is enriched in domains distinct from CeVPS-27 and CeVPS-23 at the endosomal membrane of epithelial cells. Biol Cell, 101 (10) 599-615.
Pilipiuk, J., Lefebvre, C., Wiesenfahrt, T., Legouis, R. and Bossinger, O. (2009) Increased IP(3)/Ca(2+) signaling compensates depletion of LET-413/DLG-1 in C. elegans epithelial junction assembly. Dev Biol, 327 (1) 34-47.
Roudier, N. , Lefebvre, C. and Legouis, R. (2005). CeVPS-27 is an endosomal protein required for molting and endocytosis of the LDL Receptor-related Protein 1 in C. elegans. Traffic, 6, 695-705.
Legouis, R*. , Jaulin-Bastard, F., Schott, S , Borg, J-P, and Labouesse, M. (2003). Basolateral targeting by Leucine Rich Repeat domains in epithelial cells. EMBO R, 4, 1096-1102. * Corresponding author
McMahon, L., Legouis, R. , Vonesch, J.L. and Labouesse, M. (2001). Assembly of C. elegans apical junctions involves compaction by LET-413 and protein aggregation by the MAGUK protein DLG-1. J. Cell Sci, 114, 2265-77. Cette publication a reçu le "Journal of Cell Science Best Paper Award 2001".
Legouis, R., Gansmuller, A., Sookhareea, S., Bosher, J. M., Baillie, D.L. and Labouesse, M. (2000). LET-413 is a basolateral protein required for the assembly of adherens junctions in C. elegans. Nature Cell Biol, 2, 415-22.
