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J Cell Biol. 2014 Oct 13;207(1):73-89. doi: 10.1083/jcb.201401137. Epub 2014 Oct 6.

Dynamin and endocytosis are required for the fusion of osteoclasts and myoblasts.

Author information

1
Department of Medicine, Harvard Medical School, Boston, MA 02115 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
2
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.
3
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.
4
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.

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.

PMID:
25287300
PMCID:
PMC4195819
DOI:
10.1083/jcb.201401137
[Indexed for MEDLINE]
Free PMC Article
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