Nap1-mediated actin remodeling is essential for mammalian myoblast fusion Journal Article

Authors: Nowak, S. J.; Nahirney, P. C.; Hadjantonakis, A. K.; Baylies, M. K.
Article Title: Nap1-mediated actin remodeling is essential for mammalian myoblast fusion
Abstract: Myoblast fusion is crucial for the formation, growth, maintenance and regeneration of healthy skeletal muscle. Unfortunately, the molecular machinery, cell behaviors, and membrane and cytoskeletal remodeling events that govern fusion and myofiber formation remain poorly understood. Using time-lapse imaging approaches on mouse C2C12 myoblasts, we identify discrete and specific molecular events at myoblast membranes during fusion and myotube formation. These events include rearrangement of cell shape from fibroblast to spindle-like morphologies, changes in lamellipodial and filopodial extensions during different periods of differentiation, and changes in membrane alignment and organization during fusion. We find that actin-cytoskeleton remodeling is crucial for these events: pharmacological inhibition of F-actin polymerization leads to decreased lamellipodial and filopodial extensions and to reduced myoblast fusion. Additionally, shRNA-mediated inhibition of Nap1, a member of the WAVE actin-remodeling complex, results in accumulations of F-actin structures at the plasma membrane that are concomitant with a decrease in myoblast fusion. Our data highlight distinct and essential roles for actin cytoskeleton remodeling during mammalian myoblast fusion, provide a platform for cellular and molecular dissection of the fusion process, and suggest a functional conservation of Nap1-regulated actin-cytoskeleton remodeling during myoblast fusion between mammals and Drosophila.
Keywords: controlled study; unclassified drug; nonhuman; animal cell; mouse; mammalia; actin; cell differentiation; cell membrane; fibroblast; cell shape; protein structure; f actin; cytoskeleton; short hairpin rna; live imaging; protein polymerization; cell-cell fusion; muscle actin; myoblast fusion; nck associated protein 1; regulator protein; cell fusion; filopodium; lamellipodium; myoblast; myotube
Journal Title: Journal of Cell Science
Volume: 122
Issue: 18
ISSN: 0021-9533
Publisher: Company of Biologists  
Date Published: 2009-09-15
Start Page: 3282
End Page: 3293
Language: English
DOI: 10.1242/jcs.047597
PROVIDER: scopus
PMCID: PMC2736864
PUBMED: 19706686
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: JNCSA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Scott J Nowak
    6 Nowak
  2. Mary K Baylies
    75 Baylies