laboratoire de physique statistique
 
 
laboratoire de physique statistique

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2015
Protein Crowding Is a Determinant of Lipid Droplet Protein Composition - Kory, Nora and Thiam, Abdou-Rachid and Farese, Jr., Robert V. and Walther, Tobias C.
DEVELOPMENTAL CELL 34351-363 (2015)

Abstract : Lipid droplets (LDs) are lipid storage organelles that grow or shrink, depending on the availability of metabolic energy. Proteins recruited to LDs mediate many metabolic functions, including phosphatidylcholine and triglyceride synthesis. How the LD protein composition is tuned to the supply and demand for lipids remains unclear. We show that LDs, in contrast to other organelles, have limited capacity for protein binding. Consequently, macromolecular crowding plays a major role in determining LD protein composition. During lipolysis, when LDs and their surfaces shrink, some, but not all, proteins become displaced. In vitro studies show that macromolecular crowding, rather than changes in monolayer lipid composition, causes proteins to fall off the LD surface. As predicted by a crowding model, proteins compete for binding to the surfaces of LDs. Moreover, the LD binding affinity determines protein localization during lipolysis. Our findings identify protein crowding as an important principle in determining LD protein composition.
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis - Wassef, Michel and Rodilla, Veronica and Teissandier, Aurelie and Zeitouni, Bruno and Gruel, Nadege and Sadacca, Benjamin and Irondelle, Marie and Charruel, Margaux and Ducos, Bertrand and Michaud, Audrey and Caron, Matthieu and Marangoni, Elisabetta and Chavrier, Philippe and Le Tourneau, Christophe and Kamal, Maud and Pasmant, Eric and Vidaud, Michel and Servant, Nicolas and Reyal, Fabien and Meseure, Dider and Vincent-Salomon, Anne and Fre, Silvia and Margueron, Raphael
GENES \& DEVELOPMENT 292547-2562 (2015)

Abstract : Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.
 
2014
Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization - Chalbi, Myriam and Barraud-Lange, Virginie and Ravaux, Benjamin and Howan, Kevin and Rodriguez, Nicolas and Soule, Pierre and Ndzoudi, Arnaud and Boucheix, Claude and Rubinstein, Eric and Wolf, Jean Philippe and Ziyyat, Ahmed and Perez, Eric and Pincet, Frederic and Gourier, Christine
DEVELOPMENT 1413732-3739 (2014)

Abstract : Little is known about the molecular mechanisms that induce gamete fusion during mammalian fertilization. After initial contact, adhesion between gametes only leads to fusion in the presence of three membrane proteins that are necessary, but insufficient, for fusion: Izumo1 on sperm, its receptor Juno on egg and Cd9 on egg. What happens during this adhesion phase is a crucial issue. Here, we demonstrate that the intercellular adhesion that Izumo1 creates with Juno is conserved in mouse and human eggs. We show that, along with Izumo1, egg Cd9 concomitantly accumulates in the adhesion area. Without egg Cd9, the recruitment kinetics of Izumo1 are accelerated. Our results suggest that this process is conserved across species, as the adhesion partners, Izumo1 and its receptor, are interchangeable between mouse and human. Our findings suggest that Cd9 is a partner of Juno, and these discoveries allow us to propose a new model of the molecular mechanisms leading to gamete fusion, in which the adhesion-induced membrane organization assembles all key players of the fusion machinery.