Journal article - Includes Student Work
Caenorhabditis elegans small heat-shock protein HSP-12.6 has a highly specialized protective function towards muscle thick filaments in vivo
Philosophical transactions of the Royal Society of London. Series B. Biological sciences, v 381(1960), 20250362
01 Oct 2026
PMID: 42817627
Featured in Collection : Drexel's Newest Publications
Abstract
Small heat-shock proteins (sHSPs) are an ancient and diverse class of molecular chaperones, acting as a first line of defence against proteotoxic stresses. While the canonical sHSPs prevent uncontrollable aggregation of a broad range of non-native substrates, a subset of sHSPs do not exhibit this broad activity in vitro, and their functions in vivo are poorly understood. Interestingly, several such sHSPs are selectively expressed in muscle tissues, including by myogenic programmes, indicating probable functional roles. We examined in vivo function of Caenorhabditis elegans HSP-12.6, which possesses no chaperone activity in vitro but regulates lifespan, and is developmentally induced in the muscles of long-lived dauer animals. We found that HSP-12.6 exhibits exceptional selectivity in protecting the muscle function against folding or assembly mutations in thick filament proteins, but not in thin filament or non-filament proteins. This selectivity paralleled its exclusive chaperone-like binding to either the healthy myosin-containing thick filaments or their aggregates. HSP-12.6 did not bind other muscle structures or aggregates, including those of thin filaments, and retained its selectivity when challenged with a toxic aggregation-prone polyQ protein. Our data establish that HSP-12.6 has a highly selective myoprotective activity, with a client spectrum distinct from other sHSPs. This article is part of the Theo Murphy meeting issue ‘ProteostaSys: a systems view of proteostasis’.
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Details
- Title
- Caenorhabditis elegans small heat-shock protein HSP-12.6 has a highly specialized protective function towards muscle thick filaments in vivo
- Creators
- Abigail Fern - Drexel UniversityJasmine Alexander-Floyd - Drexel UniversityAnhelina Volchok - University of OxfordSusan M. Cahill - Drexel UniversitySrikar Donepudi - Rutgers, The State University of New JerseyJana Smuts - Drexel UniversityTali Gidalevitz (Corresponding Author) - Drexel University
- Publication Details
- Philosophical transactions of the Royal Society of London. Series B. Biological sciences, v 381(1960), 20250362
- Publisher
- The Royal Society
- Number of pages
- 12
- Grant note
- R36: AG045411 Louis and Bessie Stein Family Fellowship
We are grateful to Drs Morimoto, Ruvinsky and Bott (Northwestern University); Nussbaum (LMU Munich) and Ben-Zvi (Ben-Gurion University) for helpful discussions; to Drs Morimoto and Nussbaum for sharing strains and Dr Rodriguez (UTHSA) for generating the HSP-12.6::mCherry strain. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Confocal imaging was conducted at Drexel University's Cell Imaging Center, RRID:SCR_022689.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:001890334400001
- Other Identifier
- 991022237301904721