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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / genetics*
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Actin Cytoskeleton / metabolism
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Actins / metabolism
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cell Differentiation
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / growth & development
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Gene Expression Regulation, Developmental
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Mice
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Muscle Development / genetics*
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Muscle Development / physiology
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Myocardium / metabolism
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Myofibrils / genetics
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Myofibrils / metabolism
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Myosins / genetics
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Sarcomeres / genetics*
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Sarcomeres / physiology
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Sarcomeres / ultrastructure
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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DAAM protein, Drosophila
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Drosophila Proteins
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Myosins
Grants and funding
This work was supported by the Hungarian Scientific Research Foundation (OTKA grants K82039 and K109330 to JM, PD83648 and K109689 to BB, OTKA NN107776 to MN). IM was a recipient of a studentship from the Hungarian Academy of Sciences. BB is a Bolyai Fellow of the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.