Nematode heat-shock protein HSP-12.6 selectively protects muscle thick filaments in vivo

In the nematode Caenorhabditis elegans, the small heat-shock protein HSP-12.6 regulates lifespan and is induced in the muscles of long-lived dauer animals. Although canonical small heat-shock proteins target a broad range of substrates, HSP-12.6 lacks chaperone activity in vitro. Researchers examined the function of HSP-12.6 in vivo to understand its physiological role. They found that HSP-12.6 specifically preserved muscle function against folding and assembly mutations in thick filament proteins. It showed no protective effect against mutations in thin filament or non-filament proteins. This selectivity corresponded to the chaperone binding exclusively to healthy myosin-containing thick filaments or their aggregates. HSP-12.6 avoided other muscle structures and maintained this strict specificity even when animals were challenged with a toxic, aggregation-prone polyQ protein.