Sarcomeric actin organization is synergistically promoted by tropomodulin, ADF/cofilin, AIP1, and profilin in C. elegans

• Type of Material: Article
• Authors: Sawako Yamashiro, Emory University; Elisabeth A. Cox, University of Wisconsin; David L. Baillie, Simon Fraser University; Jeff D. Hardin, University of Wisconsin; Shoichiro Ono, Emory University
• Language: English
• Date: 2008-12-01
• Publisher: Company of Biologists
• Publication Version: Final Published Version
• Copyright Statement: © The Company of Biologists LTD
• Final Published Version (URL): http://jcs.biologists.org/content/121/23/3867.long
• Title of Journal or Parent Work: Journal of Cell Science
• ISSN: 0021-9533
• Volume: 121
• Issue: Pt 23
• Start Page: 3867
• End Page: 3877
• Grant/Funding Information: This work was supported by grants from NSERC (Canada) and CIHR (Canada) to D. L. B., National Institute of Health grant GM058038 and a grant from Muscular Dystrophy Association to J. D. H., and National Institute of Health grant AR48615 to S. O.
• Keywords: striated muscle; Actin dynamics; pointed end; myofibrils
• Research Categories: Biology, Cell; Health Sciences, Pathology; Chemistry, Biochemistry

Abstract

Sarcomeric organization of thin and thick filaments in striated muscle is important for efficient generation of contractile forces. Sarcomeric actin filaments are uniform in their lengths and regularly arranged in a striated pattern. Tropomodulin caps the pointed end of actin filaments and is a critical regulator of sarcomere assembly. Here, we report unexpected synergistic functions of tropomodulin with enhancers of actin filament dynamics in Caenorhabditis elegans striated muscle. Pointed-end capping by tropomodulin inhibited actin filament depolymerization by ADF/cofilin in vitro. However, in vivo, depletion of tropomodulin strongly enhanced disorganization of sarcomeric actin filaments in ADF/cofilin mutants, rather than antagonistically suppressing the phenotype. Similar phenotypic enhancements by tropomodulin depletion were also observed in mutant backgrounds for AIP1 and profilin. These in vivo effects cannot be simply explained by antagonistic effects of tropomodulin and ADF/cofilin in vitro. Thus, we propose a model in which tropomodulin and enhancers of actin dynamics synergistically regulate elongation and shortening of actin filaments at the pointed end.