Myogenesis involves the iterative fusion of myoblasts into muscle fibres that is mediated by actin nucleation and polymerisation at the fusion site. In Drosophila embryos, fusion occurs between two distinct sets of myoblasts: founder cells, which determine a specific muscle identity, and fusion-competent cells that act as fusion mass and allow growth into syncytial muscle fibres. However, it is not understood how these iterative rounds of cell–cell fusion are regulated at the subcellular level. In this study (Drechsler et al., 2018), Maik Drechsler, Achim Paululat and co-workers now identify Fizzy related (Fzr), an adaptor of the large E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) in a screen for factors that induce aberrant heart and muscle morphologies in fly embryos. Detailed analysis of fzr mutants indicates that myoblast fusion is inhibited and smaller F-actin foci are present at the fusion site. Interestingly, this effect is distinct from an over-proliferation phenotype, pointing to a new cell-cycle-independent function of Fzr during myogenesis. The authors further observe an accumulation of the fusion proteins Rolling pebbles (Rols) and Dumbfounded (Duf) in fzr mutants, and demonstrate that APC/C directly targets Duf through its D-boxes to mediate its proteasomal degradation. These findings thus provide the first evidence for a myogenic role of APC/C and further work will be necessary to fully characterise this unexpected function.
