title: The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway.
abstract: The four related mammalian MEX-3 RNA-binding proteins are evolutionarily conserved molecules for which the in vivo functions have not yet been fully characterized. Here, we report that male mice deficient for the gene encoding Mex3b are subfertile. Seminiferous tubules of Mex3b-deficient mice are obstructed as a consequence of the disrupted phagocytic capacity of somatic Sertoli cells. In addition, both the formation and the integrity of the blood-testis barrier are compromised owing to mislocalization of N-cadherin and connexin 43 at the surface of Sertoli cells. We further establish that Mex3b acts to regulate the cortical level of activated Rap1, a small G protein controlling phagocytosis and cell-cell interaction, through the activation and transport of Rap1GAP. The active form of Rap1 (Rap1-GTP) is abnormally increased at the membrane cortex and chemically restoring Rap1-GTP to physiological levels rescues the phagocytic and adhesion abilities of Sertoli cells. Overall, these findings implicate Mex3b in the spatial organization of the Rap1 pathway that orchestrates Sertoli cell functions.
authors.affiliation: INSERM, U823; Université Joseph Fourier-Grenoble 1; Institut Albert Bonniot, Grenoble F-38700, France.
authors.forename: Maïlys
authors.initials: M
authors.lastname: Le Borgne
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartier
authors.forename: Karine
authors.initials: K
authors.lastname: Buchet-Poyau
authors.forename: Olivier
authors.initials: O
authors.lastname: Destaing
authors.forename: Eva
authors.initials: E
authors.lastname: Faurobert
authors.forename: Chantal
authors.initials: C
authors.lastname: Thibert
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rouault
authors.forename: Julien
authors.initials: J
authors.lastname: Courchet
authors.forename: Didier
authors.initials: D
authors.lastname: Nègre
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
authors.forename: Corinne
authors.initials: C
authors.lastname: Albiges-Rizo
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.forename: Dominique
authors.initials: D
authors.lastname: Segretain
authors.forename: Pascale
authors.initials: P
authors.lastname: Crépieux
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Perrard
authors.forename: Marc
authors.initials: M
authors.lastname: Billaud
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012670:Seminiferous Epithelium / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014018:Tissue Distribution / Q000235:genetics; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000589341:MEX3B protein, mouse; D016601:RNA-Binding Proteins; D020827:rap1 GTP-Binding Proteins
keywords: MEX-3; Mouse; Phagocytosis; RNA-binding proteins; Rap1; Sertoli cell