Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan; Department of Molecular Neurobiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan; Laboratory of Molecular and Cellular Biology, Graduate School of Science and Engineering for Research, University of Toyama, Toyama, Japan
Masashi Tachikawa
Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan
Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan; National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan
Takuya Okada
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan; Department of Molecular Neurobiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan; National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan
Kazuko Keino-Masu
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan; Department of Molecular Neurobiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan; Department of Molecular Neurobiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
Membranes undergo various patterns of deformation during vesicle fusion, but how this membrane deformation is regulated and contributes to fusion remains unknown. In this study, we developed a new method of observing the fusion of individual late endosomes and lysosomes by using mouse yolk sac visceral endoderm cells that have huge endocytic vesicles. We found that there were two distinct fusion modes that were differently regulated. In homotypic fusion, two late endosomes fused quickly, whereas in heterotypic fusion they fused to lysosomes slowly. Mathematical modeling showed that vesicle size is a critical determinant of these fusion types and that membrane fluctuation forces can overcome the vesicle size effects. We found that actin filaments were bound to late endosomes and forces derived from dynamic actin remodeling were necessary for quick fusion during homotypic fusion. Furthermore, cofilin played a role in endocytic fusion by regulating actin turnover. These data suggest that actin promotes vesicle fusion for efficient membrane trafficking in visceral endoderm cells.
