DAAM is required for thin filament formation and Sarcomerogenesis during muscle development in Drosophila

• Published in: PLoS genetics Vol. 10; no. 2; p. e1004166
• Main Authors: Molnár, Imre, Migh, Ede, Szikora, Szilárd, Kalmár, Tibor, Végh, Attila G, Deák, Ferenc, Barkó, Szilvia, Bugyi, Beáta, Orfanos, Zacharias, Kovács, János, Juhász, Gábor, Váró, György, Nyitrai, Miklós, Sparrow, John, Mihály, József
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-02-2014; Public Library of Science (PLoS)
• Subjects: Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Actins - metabolism; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animal development; Animals; Biology; Cell Differentiation; Cytoskeleton; Drosophila; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Gene Expression Regulation, Developmental; Genetic aspects; Heart; Insects; Mice; Muscle Development - genetics; Muscle Development - physiology; Muscles; Muscular system; Myocardium - metabolism; Myofibrils - genetics; Myofibrils - metabolism; Myosins - genetics; Physiological aspects; Proteins; Sarcomeres - genetics; Sarcomeres - physiology; Sarcomeres - ultrastructure; Hungary
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004166

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.