title: Stabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration.
abstract: Myoblast fusion is essential for the formation of skeletal muscle myofibres. Studies have shown that phosphatidylserine is necessary for myoblast fusion, but the underlying mechanism is not known. Here we show that the phosphatidylserine receptor stabilin-2 acts as a membrane protein for myoblast fusion during myogenic differentiation and muscle regeneration. Stabilin-2 expression is induced during myogenic differentiation, and is regulated by calcineurin/NFAT signalling in myoblasts. Forced expression of stabilin-2 in myoblasts is associated with increased myotube formation, whereas deficiency of stabilin-2 results in the formation of small, thin myotubes. Stab2-deficient mice have myofibres with small cross-sectional area and few myonuclei and impaired muscle regeneration after injury. Importantly, myoblasts lacking stabilin-2 have reduced phosphatidylserine-dependent fusion. Collectively, our results show that stabilin-2 contributes to phosphatidylserine-dependent myoblast fusion and provide new insights into the molecular mechanism by which phosphatidylserine mediates myoblast fusion during muscle growth and regeneration.
authors.affiliation: Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Seung-Yoon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Youngeun
authors.initials: Y
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Convergence Medicine, University of Ulsan, College of Medicine &Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Korea Institute Science and Technology, Seoul 136-791, Republic of Korea.|KU-KIST school, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002459:Cell Fusion; D002460:Cell Line; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D010718:Phosphatidylserines; C486733:Stab2 protein, mouse