RRC ID 33073
Author Molnár I, Migh E, Szikora S, Kalmár T, Végh AG, Deák F, Barkó S, Bugyi B, Orfanos Z, Kovács J, Juhász G, Váró G, Nyitrai M, Sparrow J, Mihály J.
Title DAAM is required for thin filament formation and Sarcomerogenesis during muscle development in Drosophila.
Journal PLoS Genet
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.
Volume 10(2)
Pages e1004166
Published 2014-2-1
DOI 10.1371/journal.pgen.1004166
PMID 24586196
PMC PMC3937221
MeSH Actin Cytoskeleton / genetics* Actin Cytoskeleton / metabolism Actins / metabolism Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Animals Cell Differentiation Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / growth & development Gene Expression Regulation, Developmental Mice Muscle Development / genetics* Muscle Development / physiology Myocardium / metabolism Myofibrils / genetics Myofibrils / metabolism Myosins / genetics Sarcomeres / genetics* Sarcomeres / physiology Sarcomeres / ultrastructure
IF 5.175
Times Cited 18
Drosophila 1539R-1 1539R-2