Myoblast fusion confusion: the resolution begins

Abstract

The fusion of muscle precursor cells is a required event for proper skeletal muscle development and regeneration. Numerous proteins have been implicated to function in myoblast fusion; however, the majority are expressed in diverse tissues and regulate numerous cellular processes. How myoblast fusion is triggered and coordinated in a muscle-specific manner has remained a mystery for decades. Through the discovery of two muscle-specific fusion proteins, Myomaker and Myomerger-Minion, we are now primed to make significant advances in our knowledge of myoblast fusion. This article reviews the latest findings regarding the biology of Myomaker and Minion-Myomerger, places these findings in the context of known pathways in mammalian myoblast fusion, and highlights areas that require further investigation. As our understanding of myoblast fusion matures so does our potential ability to manipulate cell fusion for therapeutic purposes.

Keywords: Minion; Muscle development; Myoblast fusion; Myomaker; Myomerger.

Fig. 1

Schematic representation of the stages of vertebrate myoblast fusion. Membrane apposition requires cell adhesion and remodeling of the actin cytoskeleton, which is controlled in part by signaling via phosphatidylserine (PS) receptors and BAI3. Myomaker and Minion/Myomerger are proposed to act at later stages, through control of membrane remodeling events that together define fusion competence, drive fusion pore formation, and support pore expansion. Myomaker and Minion/Myomerger also define potential asymmetry in the fusion process and could require an interaction between the two proteins for fusion. The black arrows indicate pathways supported by experimental evidence, whereas red arrows depict proposed functions