title: Cleavage of the Drosophila screw prodomain is critical for a dynamic BMP morphogen gradient in embryogenesis.
abstract: Dorsoventral patterning of the Drosophila embryo is regulated by graded distribution of bone morphogenetic proteins (BMPs) composed of two ligands, decapentaplegic (Dpp) a BMP2/4 ortholog and screw (Scw) a BMP5/6/7/8 family member. scw(E1) encodes an unusual allele that was isolated as a dominant enhancer of partial loss-of-function mutations in dpp. However, the molecular mechanisms that underlie this genetic interaction remain to be addressed. Here we show that scw(E1) contains a mutation at the furin cleavage site within the prodomain that is crucial for ligand production. Furthermore, our data show that Scw(E1) preferentially forms heterodimers with Dpp rather than homotypic dimers, providing a possible explanation for the dominant negative phenotype of scw(E1) alleles. The unprocessed prodomain of Scw(E1) remains in a complex with the Dpp:Scw heterodimer, and thus could interfere with interaction of the ligand with the extracellular matrix, or the kinetics of processing/secretion of the ligand in vivo. These data reveal novel mechanisms by which post-translational regulation of Scw can modulate Dpp signaling activity.
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 65 (Viikinkaari 1), 00014 Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Künnapuu
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 65 (Viikinkaari 1), 00014 Helsinki, Finland.
authors.forename: Petra M
authors.initials: PM
authors.lastname: Tauscher
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 65 (Viikinkaari 1), 00014 Helsinki, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Tiusanen
authors.affiliation: Department of Development and Cell Biology, University of California, Irvine, CA 92697, USA.
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 65 (Viikinkaari 1), 00014 Helsinki, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Löytynoja
authors.affiliation: Department of Development and Cell Biology, University of California, Irvine, CA 92697, USA. Electronic address: karora@uci.edu.
authors.forename: Kavita
authors.initials: K
authors.lastname: Arora
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 65 (Viikinkaari 1), 00014 Helsinki, Finland. Electronic address: osamu.shimmi@helsinki.fi.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimmi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001756:Blastoderm / Q000196:embryology / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D008024:Ligands; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D008024:Ligands; D050505:Mutant Proteins; C090409:SCW protein, Drosophila; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila
keywords: Bone morphogenetic protein; Decapentaplegic (dpp); Dorsal–ventral patterning; Post-translational regulation; Proprotein convertase