DAAM Is Required for Thin Filament Formation and Sarcomerogenesis during Muscle Development in Drosophila

Imre Molnár, Ede Migh, Szilárd Szikora, Tibor Kalmár, Attila G. Végh, Ferenc Deák, Szilvia Barkó, Beáta Bugyi, Zacharias Orfanos, János Kovács, Gábor Juhász, György Váró, Miklós Nyitrai, John Sparrow, József Mihály

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Article numbere1004166
JournalPLoS genetics
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 2014

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Molnár, I., Migh, E., Szikora, S., Kalmár, T., Végh, A. G., Deák, F., Barkó, S., Bugyi, B., Orfanos, Z., Kovács, J., Juhász, G., Váró, G., Nyitrai, M., Sparrow, J., & Mihály, J. (2014). DAAM Is Required for Thin Filament Formation and Sarcomerogenesis during Muscle Development in Drosophila. PLoS genetics, 10(2), [e1004166]. https://doi.org/10.1371/journal.pgen.1004166