title: Novel function of stabilin-2 in myoblast fusion: the recognition of extracellular phosphatidylserine as a "fuse-me" signal.
abstract: Myoblast fusion is important for skeletal muscle formation. Even though the knowledge of myoblast fusion mechanism has accumulated over the years, the initial signal of fusion is yet to be elucidated. Our study reveals the novel function of a phosphatidylserine (PS) receptor, stabilin-2 (Stab2), in the modulation of myoblast fusion, through the recognition of PS exposed on myoblasts. During differentiation of myoblasts, Stab2 expression is higher than other PS receptors and is controlled by calcineurin/NFAT signaling on myoblasts. The forced expression of Stab2 results in an increase in myoblast fusion; genetic ablation of Stab2 in mice causes a reduction in muscle size, as a result of impaired myoblast fusion. After muscle injury, muscle regeneration is impaired in Stab2- deficient mice, resulting in small myofibers with fewer nuclei, which is due to reduction of fusion rather than defection of myoblast differentiation. The fusion-promoting role of Stab2 is dependent on its PS-binding motif, and the blocking of PS-Stab2 binding impairs cell-cell fusion on myoblasts. Given our previous finding that Stab2 recognizes PS exposed on apoptotic cells for sensing as an "eat-me" signal, we propose that PS-Stab2 binding is required for sensing of a "fuse-me" signal as the initial signal of myoblast fusion. [BMB Reports 2016; 49(6): 303-304].
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Go-Woon
authors.initials: GW
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792; Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 38066, Korea.
authors.forename: Seung-Yoon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792; KU-KIST School, Korea University, Seoul 02841, Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D005110:Extracellular Space / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; C486733:Stab2 protein, mouse; C408123:phosphatidylserine receptor