title: hemingway is required for sperm flagella assembly and ciliary motility in Drosophila.
abstract: Cilia play major functions in physiology and development, and ciliary dysfunctions are responsible for several diseases in humans called ciliopathies. Cilia motility is required for cell and fluid propulsion in organisms. In humans, cilia motility deficiencies lead to primary ciliary dyskinesia, with upper-airways recurrent infections, left-right asymmetry perturbations, and fertility defects. In Drosophila, we identified hemingway (hmw) as a novel component required for motile cilia function. hmw encodes a 604-amino acid protein characterized by a highly conserved coiled-coil domain also found in the human orthologue, KIAA1430. We show that HMW is conserved in species with motile cilia and that, in Drosophila, hmw is expressed in ciliated sensory neurons and spermatozoa. We created hmw-knockout flies and found that they are hearing impaired and male sterile. hmw is implicated in the motility of ciliated auditory sensory neurons and, in the testis, is required for elongation and maintenance of sperm flagella. Because HMW is absent from mature flagella, we propose that HMW is not a structural component of the motile axoneme but is required for proper acquisition of motile properties. This identifies HMW as a novel, evolutionarily conserved component necessary for motile cilium function and flagella assembly.
authors.affiliation: Centre de Génétique et de Physiologie Moléculaire et Cellulaire, UMR 5534, Centre National de la Recherche Scientifique, Université de Lyon 1, 69622 Lyon, France Department of Cellular Neurobiology, University of Göttingen, 37077 Göttingen, Germany.
authors.forename: Fabien
authors.initials: F
authors.lastname: Soulavie
authors.forename: David
authors.initials: D
authors.lastname: Piepenbrock
authors.forename: Joëlle
authors.initials: J
authors.lastname: Thomas
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vieillard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Duteyrat
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cortier
authors.forename: Anne
authors.initials: A
authors.lastname: Laurençon
authors.forename: Martin C
authors.initials: MC
authors.lastname: Göpfert
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Durand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D002923:Cilia / Q000378:metabolism*; D002925:Ciliary Motility Disorders; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D055786:Gene Knockout Techniques; D034381:Hearing Loss / Q000235:genetics; D007248:Infertility, Male; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D000071701:Regulatory Factor X Transcription Factors; D016415:Sequence Alignment; D013082:Sperm Tail / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; C000594400:hmw protein, Drosophila