Authors
Abigail Fern, Jasmine Alexander-Floyd, Anhelina Volchok, Susan M Cahill, Srikar Donepudi, Jana Smuts, Tali Gidalevitz
Published in
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. Volume 381. Issue 1960. Oct 01, 2026.
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'.
PMID:
42817627
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.
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