title: Posttranslational processing of mouse and human BMP-15: potential implication in the determination of ovulation quota.
abstract: There has been significant attention to the growing recognition that oocytes have a critical capacity to organize and govern surrounding somatic cells. Bone morphogenetic protein 15 (BMP-15) is an oocyte-secreted factor that has raised particular interest due to its established role in determining ovulation quota and female fertility in mammals. As a first step in determining whether there are species-specific differences in the BMP-15 system that may play causal roles in the differences in ovulation quota observed in different mammalian species, we here compare the molecular characteristics of BMP-15 of polyovulatory mice with that of monoovulatory humans. We found that, although human BMP-15 mature protein is readily produced, there are defects in the production of mouse BMP-15 mature protein in an in vitro system of transfected cells. The generation of chimeric constructs consisting of different combinations of mouse and human BMP-15 proregions, cleavage sites, and mature regions indicates that the defects in the production of mouse BMP-15 mature protein depend on the presence of the mouse BMP-15 proregion. The mouse proregion also caused a significant reduction in the production of human BMP-15 mature protein. The coexpression with a convertase cleavage enzyme, furin, results in complete processing of all these chimeras; however, no mouse mature protein is detected in either secreted or cell-confined forms except when associated with the human proregion. Based on the biological role of BMP-15, defects in the production of mouse BMP-15 mature protein could correlate with the high ovulation quota and litter size observed in mice.
authors.affiliation: Department of Reproductive Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093-0633, USA.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hashimoto
authors.forename: R Kelly
authors.initials: RK
authors.lastname: Moore
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimasaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055430:Bone Morphogenetic Protein 15; D002460:Cell Line; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D005260:Female; D006031:Glycosylation; D055429:Growth Differentiation Factor 9; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010060:Ovulation / Q000502:physiology*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: C525901:BMP15 protein, human; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D017077:Culture Media, Conditioned; C525897:GDF9 protein, human; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase