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1.N.2 The Myoblast Fusion Complex (MFC) Family 

Existing evidence suggests that several proteins may be involved in myoblast fusion is various systems (Schejter 2016). The principal protein constituents that could mediate myoblast pore-formatioin and fusion are (1) annexins A1 and A5, Ca2+-regulated phospholipid binding proteins (TC# 1.A.31.1.3 and, 1.7, respectively), Singles-bar (Sing) with a MARVEL domain (TC# 9.A.69.1.1), present in Drosophila, and human Myomaker, a transmembrane (7 TMS) myoblast fusogen, also known as Tmem8c, that increases fusion rates in humans, fruit flies, chickens and zebrafish (Schejter 2016). Myomaker may mediate fusioin of several types of cells in additioin to myoblasts.  In C. elegans, there are proteins called FF fusogens (TC#9.A.68.1.1) that may mediate cell fusion. Other proteins that can mediate fusion in humans are the Syncytins (TC# 1.G.9.1.1). Reviewed by Hernández and Podbilewicz 2017.

Classic mechanisms for membrane fusion involve transmembrane proteins that assemble into complexes and dynamically alter their conformation to bend membranes, leading to mixing of membrane lipids (hemifusion) and fusion pore formation. Myomaker and Myomerger (Mymk; Minion) govern myoblast fusion and muscle formation but are structurally divergent from traditional fusogenic proteins. Leikina et al. 2018 showed that Myomaker and Myomerger independently mediate distinct steps in the fusion pathway, where Myomaker is involved in membrane hemifusion and Myomerger is necessary for fusion pore formation. Myomerger is required on the cell surface where its ectodomains stress membranes, but Myomerger drives fusion completion in a heterologous system independently of Myomaker. Moreover, a Myomaker-Myomerger physical interaction is not required for function. Thus, a stepwise cell fusion mechanism in myoblasts where different proteins are delegated to perform unique membrane functions essential for membrane coalescence is suggested (Leikina et al. 2018).

References associated with 1.N.2 family:

Bi, P., A. Ramirez-Martinez, H. Li, J. Cannavino, J.R. McAnally, J.M. Shelton, E. Sánchez-Ortiz, R. Bassel-Duby, and E.N. Olson. (2017). Control of muscle formation by the fusogenic micropeptide myomixer. Science 356: 323-327. 28386024
Goh, Q. and D.P. Millay. (2017). Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy. Elife 6:. 28186492
Hernández, J.M. and B. Podbilewicz. (2017). The hallmarks of cell-cell fusion. Development 144: 4481-4495. 29254991
Jia, X., H. Lin, B.A. Abdalla, and Q. Nie. (2016). Characterization of miR-206 Promoter and Its Association with Birthweight in Chicken. Int J Mol Sci 17: 559. 27089330
Landemaine, A., P.Y. Rescan, and J.C. Gabillard. (2014). Myomaker mediates fusion of fast myocytes in zebrafish embryos. Biochem. Biophys. Res. Commun. 451: 480-484. 25078621
Leikina, E., D.G. Gamage, V. Prasad, J. Goykhberg, M. Crowe, J. Diao, M.M. Kozlov, L.V. Chernomordik, and D.P. Millay. (2018). Myomaker and Myomerger Work Independently to Control Distinct Steps of Membrane Remodeling during Myoblast Fusion. Dev Cell. [Epub: Ahead of Print] 30197239
Peng, S.P., X.L. Li, L. Wang, J. Ou-Yang, J. Ma, L.L. Wang, H.Y. Liu, M. Zhou, Y.L. Tang, W.S. Li, X.M. Luo, L. Cao, K. Tang, S.R. Shen, and G.Y. Li. (2006). The role of NGX6 and its deletion mutants in the proliferation, adhesion and migration of nasopharyngeal carcinoma 5-8F cells. Oncology 71: 273-281. 17641538
Schejter, E.D. (2016). Myoblast fusion: Experimental systems and cellular mechanisms. Semin Cell Dev Biol. [Epub: Ahead of Print] 27423913
Zhang, W. and S. Roy. (2017). Myomaker is required for the fusion of fast-twitch myocytes in the zebrafish embryo. Dev Biol 423: 24-33. 28161523