Mutations in caenorhabditis elegans actin, which are equivalent to human cardiomyopathy mutations, cause abnormal actin aggregation in nematode striated muscle

• Type of Material: Article
• Authors: Y Hayashi, Emory University; Kanako Ono, Emory University; Shoichiro Ono, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: F1000Research
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Hayashi Y et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.12688/f1000research.18476.1
• Title of Journal or Parent Work: F1000Research
• ISSN: 2046-1402
• Volume: 8
• Start Page: 279
• End Page: 279
• Grant/Funding Information: This work was supported by a grant from the National Institutes of Health (AR048615) to S.O.; The C. elegans strain N2 was provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440).
• Keywords: aggregates; sarcomere; actin; myofibrils; cardiomyopathy
• Research Categories: Health Sciences, Oncology; Biology, Cell; Health Sciences, Pathology

Abstract

Actin is a central component of muscle contractile apparatuses, and a number of actin mutations cause diseases in skeletal, cardiac, and smooth muscles. However, many pathogenic actin mutations have not been characterized at cell biological and physiological levels. In this study, we tested whether the nematode Caenorhabditis elegans could be used to characterize properties of actin mutants in muscle cells in vivo. Two representative actin mutations, E99K and P164A, which cause hypertrophic cardiomyopathy in humans, are introduced in a muscle-specific C. elegans actin ACT-4 as E100K and P165A, respectively. When green fluorescent protein-tagged wild-type ACT-4 (GFP-ACT-4), is transgenically expressed in muscle at low levels as compared with endogenous actin, it is incorporated into sarcomeres without disturbing normal structures. GFP-ACT-4 variants with E100K and P165A are incorporated into sarcomeres, but also accumulated in abnormal aggregates, which have not been reported for equivalent actin mutations in previous studies. Muscle contractility, as determined by worm motility, is not apparently affected by expression of ACT-4 mutants. Our results suggest that C. elegans muscle is a useful model system to characterize abnormalities caused by actin mutations.