title: DAAM is required for thin filament formation and Sarcomerogenesis during muscle development in Drosophila.
abstract: During muscle development, myosin and actin containing filaments assemble into the highly organized sarcomeric structure critical for muscle function. Although sarcomerogenesis clearly involves the de novo formation of actin filaments, this process remained poorly understood. Here we show that mouse and Drosophila members of the DAAM formin family are sarcomere-associated actin assembly factors enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and the heart. We found that loss of dDAAM function results in multiple defects in sarcomere development including thin and thick filament disorganization, Z-disc and M-band formation, and a near complete absence of the myofibrillar lattice. Collectively, our data suggest that dDAAM is required for the initial assembly of thin filaments, and subsequently it promotes filament elongation by assembling short actin polymers that anneal to the pointed end of the growing filaments, and by antagonizing the capping protein Tropomodulin.
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Molnár
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: Ede
authors.initials: E
authors.lastname: Migh
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: Szilárd
authors.initials: S
authors.lastname: Szikora
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kalmár
authors.affiliation: Institute of Biophysics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: Attila G
authors.initials: AG
authors.lastname: Végh
authors.affiliation: Institute of Biochemistry, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Deák
authors.affiliation: University of Pécs, Department of Biophysics, Pécs, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Barkó
authors.affiliation: University of Pécs, Department of Biophysics, Pécs, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Bugyi
authors.affiliation: Department of Biology, University of York, York, United Kingdom.
authors.forename: Zacharias
authors.initials: Z
authors.lastname: Orfanos
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Kovács
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.affiliation: Institute of Biophysics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Váró
authors.affiliation: University of Pécs, Department of Biophysics, Pécs, Hungary ; Hungarian Academy of Sciences, Office for Subsidized Research Units, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Nyitrai
authors.affiliation: Department of Biology, University of York, York, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Sparrow
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Mihály
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics* / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D024510:Muscle Development / Q000235:genetics* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000235:genetics / Q000378:metabolism; D009218:Myosins / Q000235:genetics; D012518:Sarcomeres / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C509803:DAAM protein, Drosophila; D029721:Drosophila Proteins; D009218:Myosins