title: Neprilysin 4, a novel endopeptidase from Drosophila melanogaster, displays distinct substrate specificities and exceptional solubility states.
abstract: Proteins belonging to the family of neprilysins are typically membrane bound M13 endopeptidases responsible for the inactivation and/or activation of peptide signaling events on cell surfaces. Mammalian neprilysins are known to be involved in the metabolism of various regulatory peptides especially in the nervous, immune, cardiovascular and inflammatory systems. Although there is still much to learn about their participation in various diseases, they are potential therapeutic targets. Here we report on the identification and first characterization of neprilysin 4 (NEP4) from Drosophila melanogaster. Reporter lines as well as in situ hybridization combined with immunolocalization demonstrated NEP4 expression during embryogenesis in pericardial cells, muscle founder cells, glia cells and male gonads. Western blot analysis confirmed the prediction of one membrane bound and one soluble isoform, a finding quite unusual among neprilysins with presumably strong physiological relevance. At least one NEP4 isoform was found in every developmental stage indicating protein activities required throughout the whole life cycle of Drosophila. Heterologously expressed NEP4 exhibited substrate preferences comparable to human neprilysin 2 with distinct cleavage of substance P and angiotensin I.
authors.affiliation: Department of Zoology/Developmental Biology, University of Osnabrück, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Meyer
authors.forename: Mareike
authors.initials: M
authors.lastname: Panz
authors.forename: Monika
authors.initials: M
authors.lastname: Zmojdzian
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jagla
authors.forename: Achim
authors.initials: A
authors.lastname: Paululat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D016415:Sequence Alignment; D012995:Solubility; D013379:Substrate Specificity
chemical_list: D029721:Drosophila Proteins; D020033:Protein Isoforms; D015260:Neprilysin