Mutual dependence between tropomodulin and tropomyosin in the regulation of sarcomeric actin assembly in Caenorhabditis elegans striated muscle

• Type of Material: Article
• Authors: Shoichiro Ono, Emory University; Mario Lewis, Emory University; Kanako Ono, Emory University
• Language: English
• Date: 2022-04-01
• Publisher: ELSEVIER GMBH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 The Authors. Published by Elsevier GmbH.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ejcb.2022.151215
• Title of Journal or Parent Work: EUROPEAN JOURNAL OF CELL BIOLOGY
• Volume: 101
• Issue: 2
• Start Page: 151215
• End Page: 151215
• Grant/Funding Information: This work was supported by a grant from the National Institutes of Health (AR048615) to S. O.
• Keywords: Life Sciences & Biomedicine; Actin; C. ELEGANS; EXPRESSION; PROTEIN; ADF/COFILIN; MYOFIBRILS; CONTRACTION; Sarcomere; Muscle; THIN FILAMENT LENGTH; Tropomyosin; Cell Biology; Tropomodulin; ISOFORMS; Science & Technology; MUTATIONS; POINTED-END

Abstract

Tropomodulin and tropomyosin are important components of sarcomeric thin filaments in striated muscles. Tropomyosin decorates the side of actin filaments and enhances tropomodulin capping at the pointed ends of the filaments. Their functional relationship has been extensively characterized in vitro, but in vivo and cellular studies in mammals are often complicated by the presence of functionally redundant isoforms. Here, we used the nematode Caenorhabditis elegans, which has a relatively simple composition of tropomodulin and tropomyosin genes, and demonstrated that tropomodulin (unc-94) and tropomyosin (lev-11) are mutually dependent on each other in their sarcomere localization and regulation of sarcomeric actin assembly. Mutation of tropomodulin caused sarcomere disorganization with formation of actin aggregates. However, the actin aggregation was suppressed when tropomyosin was depleted in the tropomodulin mutant. Tropomyosin was mislocalized to the actin aggregates in the tropomodulin mutants, while sarcomere localization of tropomodulin was lost when tropomyosin was depleted. These results indicate that tropomodulin and tropomyosin are interdependent in the regulation of organized sarcomeric assembly of actin filaments in vivo.