During development and under non-stress conditions, the Hsp90 co-chaperone UNC-45 (purple/grey shape) folds and assembles myosin (grey shapes) into growing myofilaments (parallel white stripes in body wall muscle cells) in muscle. During OptIMMuS-induced mechanical stress, the E3 ubiquitin ligase NHL-1 (green rectangle with rounded corners) and its binding partner F40A3.6 (blue circle) accumulate near UNC-45 in contracting muscle and locally assist in myofilament repair of misfolded myosin molecules. In conditional myosin loss-of-function mutants, which exhibit global myosin misfolding (red jagged shapes) and myofilament disorganization (wavy white stripes in body wall muscle cells), elevated levels of NHL-1 regulate myosin protein amount and functionality through ubiquitylation. Missense mutations in UNC-45 (yellow asterisks), each uniquely affecting the chaperoning function of UNC-45 and resulting in myosin misfolding, suggest that the interaction of UNC-45, NHL-1, and F40A3.6 is required for myosin regulation.
