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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., Competing Interests: SK, MT, MT, TO, TN, KK, MM No competing interests declared, (© 2024, Koike et al.)

Autotaxin, encoded by the Enpp2 gene, produces lysophosphatidic acid (LPA), which exerts numerous biological functions via its cognate receptors. Enpp2 null mutant mice die by embryonic day 9.5 owing to aberrant vascular development in the yolk sac, preventing analysis after that period. In this study, we found that Enpp2 heterozygous mice in the DBA/2 genetic background showed an eye-open-at-birth phenotype at high frequency, caused by failure of eyelid closure during the embryonic stage. Notably, wildtype pups from the Enpp2 heterozygous dam showed the phenotype, although at lower frequency, suggesting that maternal LPA affects the embryonic development., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)