title: Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization.
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.
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique UMR8550, 24 rue Lhomond, Paris 75005, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Chalbi
authors.affiliation: Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale U1016, Génomique, Epigénétique et Physiopathologie de la Reproduction, Service d'Histologie Embryologie Biologie de la Reproduction-CECOS, Hopital Cochin, AP-HP24 rue du Faubourg Saint-Jacques, Paris 75014, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Barraud-Lange
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique UMR8550, 24 rue Lhomond, Paris 75005, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ravaux
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique UMR8550, 24 rue Lhomond, Paris 75005, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Howan
authors.affiliation: Université Pierre et Marie Curie Laboratoire des biomolécules, Paris 75005, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodriguez
authors.affiliation: Université Pierre et Marie Curie Laboratoire des biomolécules, Paris 75005, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Soule
authors.affiliation: Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale U1016, Génomique, Epigénétique et Physiopathologie de la Reproduction, Service d'Histologie Embryologie Biologie de la Reproduction-CECOS, Hopital Cochin, AP-HP24 rue du Faubourg Saint-Jacques, Paris 75014, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ndzoudi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1004, 14 avenue Paul Vaillant Couturier, Villejuif 94800, France Université Paris-Sud, Institut André Lwoff, Villejuif 94800, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1004, 14 avenue Paul Vaillant Couturier, Villejuif 94800, France Université Paris-Sud, Institut André Lwoff, Villejuif 94800, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Rubinstein
authors.affiliation: Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale U1016, Génomique, Epigénétique et Physiopathologie de la Reproduction, Service d'Histologie Embryologie Biologie de la Reproduction-CECOS, Hopital Cochin, AP-HP24 rue du Faubourg Saint-Jacques, Paris 75014, France.
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Wolf
authors.affiliation: Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale U1016, Génomique, Epigénétique et Physiopathologie de la Reproduction, Service d'Histologie Embryologie Biologie de la Reproduction-CECOS, Hopital Cochin, AP-HP24 rue du Faubourg Saint-Jacques, Paris 75014, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ziyyat
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique UMR8550, 24 rue Lhomond, Paris 75005, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Perez
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique UMR8550, 24 rue Lhomond, Paris 75005, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pincet
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique UMR8550, 24 rue Lhomond, Paris 75005, France gourier@lps.ens.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Gourier
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D005260:Female; D005306:Fertilization / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D060245:Tetraspanin 29 / Q000378:metabolism*
chemical_list: C554870:Cd9 protein, mouse; D007136:Immunoglobulins; C498177:Izumo1 protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D060245:Tetraspanin 29; C543634:folate receptor 4, mouse
keywords: CD9; Fertilization; Izumo1; Juno; Membrane dynamics; Membrane organization