title: Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81.
abstract: Skeletal muscle regeneration after injury follows a remarkable sequence of synchronized events. However, the mechanisms regulating the typical organization of the regenerating muscle at different stages remain largely unknown. Here we show that muscle regeneration in mice lacking either CD9 or CD81 is abnormal and characterized by the formation of discrete giant dystrophic myofibres, which form more quickly in the absence of both tetraspanins. We also show that, in myoblasts, these two tetraspanins associate with the immunoglobulin domain molecule CD9P-1 (EWI-F/FPRP), and that grafting of CD9P-1-depleted myoblasts in regenerating muscles also leads to abnormal regeneration. In vitro myotubes lacking CD9P-1 or both CD9 and CD81 fuse with a higher frequency than normal myotubes. Our study unveils a mechanism preventing inappropriate fusion of myotubes that has an important role in the restitution of normal muscle architecture during muscle regeneration.
authors.affiliation: Inserm, 14 rue Paul Vaillant Couturier, 94807 Villejuif cedex, France. stephanie.charrin@inserm.fr
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Charrin
authors.forename: Mathilde
authors.initials: M
authors.lastname: Latil
authors.forename: Sabrina
authors.initials: S
authors.lastname: Soave
authors.forename: Anna
authors.initials: A
authors.lastname: Polesskaya
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.forename: Eric
authors.initials: E
authors.lastname: Rubinstein
mesh_terms: D000818:Animals; D002459:Cell Fusion; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D012038:Regeneration; D060225:Tetraspanin 28 / Q000502:physiology*; D060245:Tetraspanin 29 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C554870:Cd9 protein, mouse; D060225:Tetraspanin 28; D060245:Tetraspanin 29