RESUMO
Sexual reproduction consists of genome reduction by meiosis and subsequent gamete fusion. The presence of genes homologous to eukaryotic meiotic genes in archaea and bacteria suggests that DNA repair mechanisms evolved towards meiotic recombination. However, fusogenic proteins resembling those found in gamete fusion in eukaryotes have so far not been found in prokaryotes. Here, we identify archaeal proteins that are homologs of fusexins, a superfamily of fusogens that mediate eukaryotic gamete and somatic cell fusion, as well as virus entry. The crystal structure of a trimeric archaeal fusexin (Fusexin1 or Fsx1) reveals an archetypical fusexin architecture with unique features such as a six-helix bundle and an additional globular domain. Ectopically expressed Fusexin1 can fuse mammalian cells, and this process involves the additional globular domain and a conserved fusion loop. Furthermore, archaeal fusexin genes are found within integrated mobile elements, suggesting potential roles in cell-cell fusion and gene exchange in archaea, as well as different scenarios for the evolutionary history of fusexins.
Assuntos
Archaea , Eucariotos , Animais , Archaea/genética , Fusão Celular , Eucariotos/genética , Células Eucarióticas , Células Germinativas/metabolismo , MamíferosRESUMO
Fibroblast growth factor 2 (FGF2) and its receptors (FGFRs) have been described in several tissues, where they regulate cellular proliferation, differentiation, motility and apoptosis. Although FGF2/FGFRs expression in the male reproductive tract has been reported, there is scarce evidence on their presence in the female reproductive tract and their involvement in the modulation of sperm function. Therefore, the objective of this study was to determine the expression of FGF2 in the female reproductive tract and to assess the role of the FGF2/FGFRs system in the regulation of sperm physiology using the murine model. FGF2 was detected in uterus and oviduct protein extracts, and it was immunolocalized in epithelial cells of the uterus, isthmus and ampulla, as well as in the cumulus oophorus-oocyte complex. The receptors FGFR1, FGFR2, FGFR3 and FGFR4 were immunodetected in the flagellum and acrosomal region of sperm recovered from the cauda epididymis. Analysis of testis sections showed the expression of FGFRs in germ cells at different stages of the spermatogenesis, suggesting the testicular origin of the sperm FGFRs. Sperm incubation with recombinant FGF2 (rFGF2) led to increased sperm motility and velocity and to enhanced intracellular Ca2+ levels and acrosomal loss compared to the control. In conclusion, this study shows that FGF2 is expressed in tissues of the female reproductive tract. Also, the fact that functional FGFRs are present in mouse sperm and that rFGF2 affects sperm motility and acrosomal exocytosis, suggests the involvement of this system in the in vivo regulation of sperm function.
Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Genitália Feminina/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Espermatozoides/fisiologia , Animais , Feminino , Masculino , Camundongos , Testículo/metabolismoRESUMO
Lectin-glycan recognition systems play central roles in many physiologic and pathologic processes. We identified a role for galectin-1 (Gal-1), a highly conserved glycan-binding protein, in the control of sperm function. We found that Gal-1 is expressed in the epididymis and associates with sperm during epididymal maturation. Exposure of sperm to Gal-1 resulted in glycan-dependent modulation of the acrosome reaction (AR), a key event in the fertilization process. Gal-1-deficient (Lgals1(-/-)) mice revealed the essential contribution of this lectin for full sperm fertilizing ability both in vitro and in vivo. Mechanistically, Lgals1(-/-) sperm exhibited defects in their ability to develop hyperactivation, a vigorous motility required for penetration of the egg vestments. Moreover, Lgals1(-/-) sperm showed a decreased ability to control cell volume and to undergo progesterone-induced AR, phenotypes that were rescued by exposure of the cells to recombinant Gal-1. Interestingly, the AR defect was associated with a deficiency in sperm membrane potential hyperpolarization. Our study highlights the relevance of the Gal-1-glycan axis in sperm function with critical implications in mammalian reproductive biology.