title: Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.
abstract: The nudel gene of Drosophila is maternally required both for structural integrity of the egg and for dorsoventral patterning of the embryo. It encodes a structurally modular protein that is secreted by ovarian follicle cells. Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development. Here we describe biochemical and immunolocalization studies that provide insight into the molecular basis for the distinct phenotypes produced by nudel mutations and for the interactions between these alleles. Mutations causing loss of embryonic dorsoventral polarity result in a failure to activate the protease domain of Nudel. Our analyses support previous findings that catalytic activity of the protease domain is required for dorsoventral patterning and that the Nudel protease is auto-activated and reveal an important role for a region adjacent to the protease domain in Nudel protease function. Mutations causing egg fragility and early embryonic arrest result in a significant decrease in extracellular Nudel protein, due to defects in post-translational processing, stability, or secretion. On the basis of these and other studies of serine proteases, we suggest potential mechanisms for the complementary and antagonistic interactions between the nudel alleles.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ellen.lemosy@att.net
authors.forename: E K
authors.initials: EK
authors.lastname: LeMosy
authors.forename: C L
authors.initials: CL
authors.lastname: Leclerc
authors.forename: C
authors.initials: C
authors.lastname: Hashimoto
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins; D047108:Embryonic Development; D006801:Humans; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019476:Insect Proteins; D012697:Serine Endopeptidases; C115869:ndl protein, Drosophila