Forcing the nuclear envelope to respond: From nuclear deformation to cell cycle progression
Whether it is generated by myosin motors or externally applied, cells are constantly subjected to mechanical tension, which profoundly impacts their growth. Mechanical tension triggers changes in cell shape, adhesion and cytoskeletal structures that control the cell-cycle machinery and orchestrate cellular rearrangements for division. As cells experience tension, the nucleus undergoes significant morphological changes due to its connection with the cytoskeleton that transmits mechanical stress to the nuclear envelope. Interestingly, recent studies indicate that forces can trigger nuclear envelope (NE) remodeling, which in turn impacts nuclear structure and function. Here we found that myosin-mediated tension causes NE deformation as cells transit from G1 to S phase. Strikingly, we show that applying compressive force on the nucleus in the absence of myosin II-mediated tension is sufficient to restore G1 to S transition. Using a combination of tools to manipulate the nuclear morphology, we observed that nuclear flattening activates a subset of transcription factors, leading to transcriptional induction of target genes that promotes G1 to S transition.
Institut of Advanced Biosciences, Université de Grenoble-Alpes