4.5 Article

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

Journal

EUROPEAN JOURNAL OF CELL BIOLOGY
Volume 101, Issue 2, Pages -

Publisher

ELSEVIER GMBH
DOI: 10.1016/j.ejcb.2022.151215

Keywords

Actin; Muscle; Sarcomere; Tropomodulin; Tropomyosin

Categories

Funding

  1. National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
  2. National Institutes of Health [AR048615]

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This study demonstrates the mutual dependence of tropomodulin and tropomyosin in sarcomere assembly and regulation of actin filaments in the nematode Caenorhabditis elegans.
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.

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