The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans.

Abstract

Mutations at the flightless-I locus (flit) of Drosophila melanogaster cause flightiessness or, when severe, incomplete ceilularization during early embryogenesis, with subsequent abnormalities in mesoderm invagination and in gastrulation. After chromosome walking, deficiency mapping, and transgenic analysis, we have isolated and characterized Oightless-I cDNAs, enabling prediction of the complete amino acid sequence of the 1256-residue protein. Data base searches revealed a homologous gene in Caenorhabditis ekgans, and we have isolated and characterized corresponding cDNAs. By using the polymerase chain reaction with nested sets of degenerate oligonucleotide primers based on conserved regions of the C. elegans and D. melanogaster proteins, we have doned a homologous human cDNA. The predicted C. ekgans and human proteins are, respectively, 49% and 58% identical to the D. melanogaster protein. The predicted proteins have signifilcant sequence similarity to the actin-binding protein gelsolin and related proteins and, in addition, have an N-terminal domain consisting of a repetitive amphipathic leucine-rich motif. This repeat is found in D. melanogaster, Saccharomyces cerevisiae, and mammalian proteins known to be involved in cell adhesion and in binding to other proteins. The structure of the maternally expressed flightless-I protein suggests that it may play a key role in embryonic cellularization by interacting with both the cytoskeleton and other cellular components. The presence of a highly conserved homologue in nematodes, flies, and humans is indicative of a fundamental role for this protein in many metazoans.

Invertebrate muscles: Thin and thick filament structure; molecular basis of contraction and its regulation, catch and asynchronous muscle

“…Drosophila thin filaments elongate from their pointed ends during myofibril development and tropomodulin regulates thin filament growth (Mardahl-Dumesnil and Fowler, 2001). Gelsolin-like proteins are present in, or affect the development of, muscle in earthworm (D'Haese and Jinssen, 1987;Giebing et al, 1994Giebing et al, , 1997, crustacea {Bock, 1994 36887 /id;Lück, 1995 36944 /id}, ascidia (Ohtsuka et al, 1994(Ohtsuka et al, , 1998Langer et al, 1998), and Drosophila, in which gelsolin is encoded by the flightless-1 gene (Campbell et al, 1993;de Couet et al, 1995). β-thymosins are present in sea urchin and scallop (Safer and Chowrashi, 1997).…”

Flightless I Homolog Negatively Modulates the TLR Pathway

“…2. Fliih was first identified as a protein involved in gastrulation and muscle degeneration in flies (30). The N-terminal region of Fliih contains 16 copies of the LRR motif, while the central and C-terminal regions are homologous to the gelsolin family of actin-binding proteins.…”

Nucleoredoxin Negatively Regulates Toll-like Receptor 4 Signaling via Recruitment of Flightless-I to Myeloid Differentiation Primary Response Gene (88)

“…It was subsequently discovered that Fli-I is conserved throughout species from nematodes to humans (10). Fli-I knock-out in mice leads to early embryonic lethality, indicating the vital importance of this molecule across species (11).…”