APC/CFzr regulates cardiac and myoblast cell numbers, and plays a crucial role during myoblast fusion

Abstract

Somatic muscles are formed by the iterative fusion of myoblasts into muscle fibres. This process is driven by the recurrent recruitment of proteins to the cell membrane to induce F-actin nucleation at the fusion site. Although several proteins involved in myoblast fusion have been identified, knowledge about their subcellular regulation is rather elusive. We identified the anaphase-promoting complex (APC/C) adaptor Fizzy related (Fzr) as an essential regulator of heart and muscle development. We show that APC/C regulates the fusion of myoblasts as well as the mitotic exit of pericardial cells, cardioblasts and myoblasts. Surprisingly, overproliferation is not causative for the observed fusion defects. Instead, mutants exhibit smaller F-actin foci at the fusion site and display reduced membrane breakdown between adjacent myoblasts. We show that lack of APC/C causes accumulation and mislocalisation of Rols and Duf, two proteins involved in the fusion process. Duf seems to serve as direct substrate of the APC/C and its destruction depends on the presence of distinct degron sequences. These novel findings indicate that protein destruction and turnover constitute major events during myoblast fusion.

Conserved Chamber-Specific Polyploidy Maintains Heart Function inDrosophila

“…Indeed, NP>fzr RNAi cardiomyocytes exhibit significantly reduced ploidy (Fig3G, FigS3E). Importantly, NP>fzr RNAi does not impact cardiomyocyte nuclear number (FigS3F), confirming that our experimental conditions do not impact the known role for fzr in controlling embryonic cardiomyocyte cell division (Drechsler et al, 2018).…”