Journal Article

Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development

Gamage, Dilani G., Goh, Qingnian, Petrany, Michael J., Quinn, Malgorzata E., Prasad, Vikram, Millay, Douglas P., Kurosaka, Mitsutoshi

2017

Overview

Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined, which has severely limited our ability to reconstitute cell fusion. Myomaker ( Tmem8c ) is a muscle-specific protein required for myoblast fusion. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-expressing fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here we show that Gm7325 , which we name myomerger, induces the fusion of myomaker-expressing fibroblasts. Thus, myomaker and myomerger together confer fusogenic activity to otherwise non-fusogenic cells. Myomerger is skeletal muscle-specific and genetic deletion in mice results in a paucity of muscle fibres demonstrating its requirement for normal muscle formation. Myomerger deficient myocytes differentiate and harbour organized sarcomeres but are fusion-incompetent. Our findings identify myomerger as a fundamental myoblast fusion protein and establish a system that begins to reconstitute mammalian cell fusion. Cellular fusion is fundamental for skeletal muscle development. Here the authors show that myomerger is expressed in myoblasts, is essential for myoblast fusion in mice, and in co-operation with myomaker confers fusogenic ability to non-fusogenic cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/51 / 38/39 / 42 / 631/136/142 / 631/136/2060/2068 / 631/532/2439 / Amino acids / Animals / Cell Communication / Cell Differentiation / Cell Fusion / Cells / Computational Biology / CRISPR-Cas Systems / Female / Fibroblasts - cytology / Humanities and Social Sciences / Male / Mammals / Membrane Proteins - physiology / Mice / Mice, Inbred C57BL / Mice, Knockout / multidisciplinary / Muscle Development / Muscle Fibers, Skeletal - physiology / Muscle Proteins - physiology / Musculoskeletal system / Myoblasts - cytology / NIH 3T3 Cells / Oligonucleotide Array Sequence Analysis / Proteins / Science / Science (multidisciplinary)