title: fussel (fuss)--A negative regulator of BMP signaling in Drosophila melanogaster.
abstract: The TGF-β/BMP signaling cascades control a wide range of developmental and physiological functions in vertebrates and invertebrates. In Drosophila melanogaster, members of this pathway can be divided into a Bone Morphogenic Protein (BMP) and an Activin-ß (Act-ß) branch, where Decapentaplegic (Dpp), a member of the BMP family has been most intensively studied. They differ in ligands, receptors and transmitting proteins, but also share some components, such as the Co-Smad Medea (Med). The essential role of Med is to form a complex with one of the two activating Smads, mothers against decapentaplegic (Mad) or dSmad, and to translocate together to the nucleus where they can function as transcriptional regulators of downstream target genes. This signaling cascade underlies different mechanisms of negative regulation, which can be exerted by inhibitory Smads, such as daughters against decapentaplegic (dad), but also by the Ski-Sno family. In this work we identified and functionally analyzed a new member of the Ski/Sno-family, fussel (fuss), the Drosophila homolog of the human functional suppressing element 15 (fussel-15). fuss codes for two differentially spliced transcripts with a neuronal expression pattern. The proteins are characterized by a Ski-Sno and a SAND homology domain. Overexpression studies and genetic interaction experiments clearly reveal an interaction of fuss with members of the BMP pathway, leading to a strong repression of BMP-signaling. The protein interacts directly with Medea and seems to reprogram the Smad pathway through its influence upon the formation of functional Mad/Medea complexes. This leads amongst others to a repression of downstream target genes of the Dpp pathway, such as optomotor blind (omb). Taken together we could show that fuss exerts a pivotal role as an antagonist of BMP signaling in Drosophila melanogaster.
authors.affiliation: Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fischer
authors.forename: Florian
authors.initials: F
authors.lastname: Bayersdorfer
authors.forename: Eva
authors.initials: E
authors.lastname: Harant
authors.forename: Renate
authors.initials: R
authors.lastname: Reng
authors.forename: Stephanie
authors.initials: S
authors.lastname: Arndt
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneuwly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D056426:Genetic Loci / Q000235:genetics; D049750:Genome, Insect / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism; D014921:Wings, Animal / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; C112504:Med protein, Drosophila; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051901:Smad4 Protein; C577215:fuss protein, Drosophila