eEF1α2 is required for actin cytoskeleton homeostasis in the aging muscle DOI Creative Commons

Hidetaka Katow,

Hyung Don Ryoo

Disease Models & Mechanisms, Journal Year: 2024, Volume and Issue: 17(9)

Published: Aug. 29, 2024

ABSTRACT The translation elongation factor eEF1α (eukaryotic 1α) mediates mRNA by delivering aminoacyl-tRNAs to ribosomes. also has other reported roles, including the regulation of actin dynamics. However, these distinct roles are often challenging uncouple and remain poorly understood in aging metazoan tissues. genomes mammals Drosophila encode two paralogs, with eEF1α1 expressed ubiquitously eEF1α2 expression more limited neurons muscle cells. Here, we report that plays a unique role maintaining myofibril homeostasis during Drosophila. Specifically, generated an null allele, which was viable showed phenotypes. In young flies, mutants had thinner myofibrils indirect flight muscles could be rescued expressing eEF1α1. With aging, mutant flies began showing abnormal distribution myosin muscles, but without change protein levels. This age-related phenotype not overexpression. These findings support unconventional myofibers.

Language: Английский

Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners DOI Creative Commons
Dávid Farkas, Szilárd Szikora,

A. S. Jijumon

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(1), P. e1011117 - e1011117

Published: Jan. 10, 2024

During striated muscle development the first periodically repeated units appear in premyofibrils, consisting of immature sarcomeres that must undergo a substantial growth both length and width, to reach their final size. Here we report that, beyond its well established role sarcomere elongation, Sarcomere short (SALS) protein is involved Z-disc formation peripheral sarcomeres. Our localization data loss-of-function studies Drosophila indirect flight strongly suggest radial initiated at Z-disc. As thin filament used powerful nanoscopy approach reveal SALS subject major conformational change during development, which might be critical stop pointed end elongation adult muscles. In addition, demonstrate roles are dependent on formin type actin assembly factors. Unexpectedly, when present excess amounts, it promotes aggregates highly resembling ones described nemaline myopathy patients. Collectively, these findings helped shed light complex mechanisms coordinated thickening sarcomeres, resulted discovery potential model, suitable for identification genetic small molecule inhibitors.

Language: Английский

Citations

2
Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission DOI Creative Commons
Briana Christophers, Shannon Leahy, David B. Soffar

et al.

Development, Journal Year: 2024, Volume and Issue: 151(13)

Published: June 13, 2024

Cofilin, an actin-severing protein, plays key roles in muscle sarcomere addition and maintenance. Our previous work found that Drosophila cofilin (DmCFL) knockdown causes progressive deterioration of structure function produces features seen nemaline myopathy caused by mutations. We hypothesized disruption actin cytoskeleton dynamics DmCFL would impact other aspects development, and, thus, conducted RNA-sequencing analysis unexpectedly revealed upregulated expression numerous neuromuscular junction (NMJ) genes. is enriched the postsynaptic compartment F-actin disorganization this subcellular domain prior to defects observed later development. Despite NMJ gene changes, we no significant changes gross presynaptic Bruchpilot active zones or total glutamate receptor levels. However, resulted mislocalization GluRIIA class receptors more deteriorated muscles strongly impaired transmission strength. These findings expand our understanding include structural development suggest may contribute pathophysiology myopathy.

Language: Английский

Citations

2
Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission DOI Creative Commons
Briana Christophers, Shannon Leahy, David B. Soffar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 22, 2023

Abstract Cofilin, an actin severing protein, plays critical roles in muscle sarcomere addition and maintenance. Our previous work has shown Drosophila cofilin ( DmCFL ) knockdown causes progressive deterioration of structure function produces features seen nemaline myopathy (NM) caused by mutations. We hypothesized that disruption cytoskeleton dynamics would impact other aspects development, and, thus, conducted RNA sequencing analysis which unexpectedly revealed upregulated expression numerous neuromuscular junction (NMJ) genes. found is enriched the postsynaptic compartment deficiency F-actin disorganization this subcellular domain prior to defects observed later development. Despite NMJ gene changes, we no significant changes gross presynaptic Bruchpilot active zones or total glutamate receptor levels. However, results mislocalization receptors containing GluRIIA subunit more deteriorated muscles neurotransmission strength strongly impaired. These findings expand our understanding cofilin’s include structural development suggest may contribute NM pathophysiology. Summary statement Cofilin regulates organization, maintenance, composition, a disease model.

Language: Английский

Citations

1
eEF1α2 is required for actin cytoskeleton homeostasis in the aging muscle DOI Creative Commons

Hidetaka Katow,

Hyung Don Ryoo

Disease Models & Mechanisms, Journal Year: 2024, Volume and Issue: 17(9)

Published: Aug. 29, 2024

ABSTRACT The translation elongation factor eEF1α (eukaryotic 1α) mediates mRNA by delivering aminoacyl-tRNAs to ribosomes. also has other reported roles, including the regulation of actin dynamics. However, these distinct roles are often challenging uncouple and remain poorly understood in aging metazoan tissues. genomes mammals Drosophila encode two paralogs, with eEF1α1 expressed ubiquitously eEF1α2 expression more limited neurons muscle cells. Here, we report that plays a unique role maintaining myofibril homeostasis during Drosophila. Specifically, generated an null allele, which was viable showed phenotypes. In young flies, mutants had thinner myofibrils indirect flight muscles could be rescued expressing eEF1α1. With aging, mutant flies began showing abnormal distribution myosin muscles, but without change protein levels. This age-related phenotype not overexpression. These findings support unconventional myofibers.

Language: Английский

Citations

0