GSE161681
Ubiquitin-dependent remodeling of the actin cytoskeleton drives cell fusion
Cell-cell fusion is a frequent and essential event during development, and its  dysregulation causes diseases ranging from infertility to muscle weakness. Fusing  cells repeatedly need to remodel their plasma membrane by orchestrated formation  and disassembly of cortical actin filaments, but how the dynamic reorganization of the    actin cytoskeleton control is still poorly understood. Here, we identified a ubiquitin-  dependent toggle switch that establishes reversible actin bundling during mammalian    cell fusion. We found that EPS8-IRSp53 complexes stabilize cortical actin bundles at  sites of cell contact, which in part pushes cells towards each other. Conversely, EPS8  monoubiquitylation by CUL3KCTD10 displaces EPS8-IRSp53 from membranes and  counteracts actin bundling, a dual activity that allows apposed cells to progress with  fusion. We conclude that cytoskeletal rearrangements during development are  precisely controlled by ubiquitylation, raising the possibility to modulate the efficiency of  cell-cell fusion for therapeutic benefit. Overall design: RNA-seq analysis was performed on undiffernitataed myoblasts cells seeded at subcondluent densities, and treated with ON-TARGETplus Non-targeting Control (Horizon Discovery; D-001810-03 UGGUUUACAUGUUUUCUGA), or ON-TARGET plus siRNA siKctd10 #1 mouse (Horizon Discovery; J-057526-05 CCAGCAAUUCUGACGAUAA)