# Regulation of actin dynamics during myofibril assembly

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $343,200

## Abstract

Project Summary
Sarcomere in striated muscle is the basic unit of contractile apparatuses. Assembly and maintenance of
organized sarcomeric structures are essential for proper contraction and relaxation in muscle. Actin is one of
the major components of sarcomeric thin filaments, and length and orientation of the filaments are precisely
regulated in striated muscle. However, the mechanism of assembly and maintenance of sarcomeric actin
filaments is complex and poorly understood. A number of regulators of actin dynamics have been identified in
skeletal muscle, and some of them are linked to genetic muscle disorders. Nemaline myopathy involves
formation of abnormal actin-rich aggregates or rods in skeletal muscle and is caused by mutations in actin or
regulators of actin dynamics. Therefore, the regulation of actin dynamics is fundamentally important for building
functional contractile apparatuses in skeletal muscle, and malfunction in this system leads to muscle disorders.
To investigate the regulatory mechanism of actin dynamics in striated muscle, we use the nematode
Caenorhabditis elegans as a model system. Body wall muscle of C. elegans is striated muscle, and most of
sarcomeric proteins are conserved between C. elegans and humans. In C. elegans, we have identified that
ADF/cofilin (UNC-60B), AIP1 (UNC-78 and AIPL-1), and cyclase-associated protein (CAS-1) enhance turnover
of actin filaments and essential for organized assembly of sarcomeric actin filaments. In addition, we identified
SUP-13 as a new regulator of muscle actin. Furthermore, we obtained evidence that the barbed ends of
sarcomeric actin filaments are aligned to previously unrecognized Z-line-like structures in C. elegans muscle.
The central hypothesis of this project is that proper site-specific regulation of actin filament dynamics is
required for assembly and maintenance of sarcomeric actin filaments. We propose three aims: (Aim 1) to
determine how sarcomeric actin assembly is regulated by ADF/cofilin, AIP1, and SUP-13, (Aim 2) to determine
how actin filament dynamics are regulated by cyclase-associated protein, and (Aim 3) to determine how
sarcomeric actin filaments are anchored near their barbed ends. We expect that results of this research will
provide new insight into the regulation of actin dynamics in striated muscle. Most of the actin-regulatory
proteins studied in this project are also expressed in mammalian skeletal muscle, and some of them are
involved in genetic muscle disorders in humans. We hope that our research in a model organism will help to
understand the conserved mechanism of myofibril assembly and maintenance under normal and pathological
conditions.

## Key facts

- **NIH application ID:** 9995378
- **Project number:** 5R01AR048615-19
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Shoichiro Ono
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,200
- **Award type:** 5
- **Project period:** 2002-05-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995378

## Citation

> US National Institutes of Health, RePORTER application 9995378, Regulation of actin dynamics during myofibril assembly (5R01AR048615-19). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9995378. Licensed CC0.

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