title: Dynamin and endocytosis are required for the fusion of osteoclasts and myoblasts.
abstract: Cell-cell fusion is an evolutionarily conserved process that leads to the formation of multinucleated myofibers, syncytiotrophoblasts and osteoclasts, allowing their respective functions. Although cell-cell fusion requires the presence of fusogenic membrane proteins and actin-dependent cytoskeletal reorganization, the precise machinery allowing cells to fuse is still poorly understood. Using an inducible knockout mouse model to generate dynamin 1- and 2-deficient primary osteoclast precursors and myoblasts, we found that fusion of both cell types requires dynamin. Osteoclast and myoblast cell-cell fusion involves the formation of actin-rich protrusions closely associated with clathrin-mediated endocytosis in the apposed cell. Furthermore, impairing endocytosis independently of dynamin also prevented cell-cell fusion. Since dynamin is involved in both the formation of actin-rich structures and in endocytosis, our results indicate that dynamin function is central to the osteoclast precursors and myoblasts fusion process, and point to an important role of endocytosis in cell-cell fusion.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
authors.forename: Nah-Young
authors.initials: NY
authors.lastname: Shin
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
authors.forename: Lynn
authors.initials: L
authors.lastname: Neff
authors.affiliation: Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510 Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510 Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ferguson
authors.affiliation: Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510 Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510 Howard Hughes Medical Institute, Chevy Chase, MD 20815.
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115 Roland_Baron@hms.harvard.edu.
authors.forename: Roland
authors.initials: R
authors.lastname: Baron
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D002459:Cell Fusion; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D034284:Dynamin I / Q000235:genetics*; D034285:Dynamin II / Q000235:genetics*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032446:Myoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering; D013234:Stem Cells
chemical_list: D034741:RNA, Small Interfering; D034284:Dynamin I; D034285:Dynamin II