title: Extracellular annexins and dynamin are important for sequential steps in myoblast fusion.
abstract: Myoblast fusion into multinucleated myotubes is a crucial step in skeletal muscle development and regeneration. Here, we accumulated murine myoblasts at the ready-to-fuse stage by blocking formation of early fusion intermediates with lysophosphatidylcholine. Lifting the block allowed us to explore a largely synchronized fusion. We found that initial merger of two cell membranes detected as lipid mixing involved extracellular annexins A1 and A5 acting in a functionally redundant manner. Subsequent stages of myoblast fusion depended on dynamin activity, phosphatidylinositol(4,5)bisphosphate content, and cell metabolism. Uncoupling fusion from preceding stages of myogenesis will help in the analysis of the interplay between protein machines that initiate and complete cell unification and in the identification of additional protein players controlling different fusion stages.
authors.affiliation: Section on Membrane Biology, Program of Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Leikina
authors.forename: Kamran
authors.initials: K
authors.lastname: Melikov
authors.forename: Sarmistha
authors.initials: S
authors.lastname: Sanyal
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Verma
authors.forename: Bokkee
authors.initials: B
authors.lastname: Eun
authors.forename: Claudia
authors.initials: C
authors.lastname: Gebert
authors.forename: Karl
authors.initials: K
authors.lastname: Pfeifer
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Lizunov
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kozlov
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Chernomordik
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism
chemical_list: D017305:Annexin A1; D017304:Annexin A5; D019269:Phosphatidylinositol 4,5-Diphosphate; C573274:annexin A1, mouse; D034281:Dynamins