To maintain the highly ordered structure of striated muscle, the polymerisation and depolymerisation of sarcomeric actin filaments must be precisely regulated. The actin-capping protein tropomodulin and the actin-depolymerising proteins ADF/cofilin and AIP1 are thought to regulate sarcomeric actin assembly – but what is the functional relationship between them? On , Shoichiro Ono and colleagues use the striated body-wall muscle of the nematode worm C. elegans to investigate the in vivo interplay between the worm tropomodulin homologue TMD-1 and other actin regulators. The authors first identify a loss-of-function TMD-1 mutant that has severely disorganised actin filaments in the body-wall muscle. In vitro, they show, TMD-1 antagonises actin depolymerisation by UNC-60B (the worm homologue of ADF/cofilin). Surprisingly, however, knocking down TMD-1 strongly enhances the disorganisation of sarcomeric actin filaments in UNC-60B mutant worms. Moreover, TMD-1 depletion has a similar effect on worms expressing mutant AIP1 or profilin. The authors conclude, therefore, that tropomodulin collaborates with ADF/cofilin, AIP1 and profilin to promote organised actin-filament assembly in sarcomeres. Their data help to decipher how sarcomeric actin is organised in vivo.
