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.
Subject(s)
RNA-Binding Proteins/physiology , Sertoli Cells/physiology , rap1 GTP-Binding Proteins/metabolism , Animals , Cells, Cultured , Embryo, Mammalian , Female , Humans , Infertility, Male/genetics , Infertility, Male/metabolism , Male , Mice , Mice, Knockout , RNA-Binding Proteins/genetics , Seminiferous Epithelium/metabolism , Sertoli Cells/metabolism , Signal Transduction , Tissue Distribution/genetics , rap1 GTP-Binding Proteins/geneticsABSTRACT
RNA-binding proteins of the evolutionarily-conserved MEX-3 family are mediators of post-transcriptional regulation in different organisms. Recent studies highlight their involvement in diverse physiological settings, including the maintenance of a balance between stem cell self-renewal and differentiation. Here, we draw attention to their putative role in tissue homeostasis and disease, particularly cancer.
