Bela M. Mulder, Roland Aufschnaiter, Antonella Russo, Roland Wedlich-Söldner, Johannes Fels, Thomas Vogl, Dietmar E. Martin, Laura Hockaday Kang, Ekaterina Menis, Wenya Hou, Julian Kuhlmann, Christopher P Dlugos, Michael M. Kessels, Mike Wälte, Kerstin C. Maier, Pauline Wales, Christian Schuberth, C. Klingner, Ireth García-Aguilar, Marco Schäfer-Herte, Johannes Roth, Hermann Pavenstädt, Britta Qualmann, Henry N. Higgs, and Annette Janning
Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in response to many physiological cues. CaAR leads to transient immobilization of organelles, drives reorganization of actin during cell cortex repair, cell spreading and wound healing, and induces long-lasting changes in gene expression. Our findings suggest that CaAR acts as fundamental facilitator of cellular adaptations in response to acute signals and stress. DOI: http://dx.doi.org/10.7554/eLife.19850.001, eLife digest Our skeleton plays a vital role in giving shape and structure to our body, it also allows us to make coordinated movements. Similarly, each cell contains a microscopic network of structures and supports called the cytoskeleton that helps cells to adopt specific shapes and is crucial for them to move around. Unlike our skeleton, which is relatively unchanging, the cytoskeleton of each cell constantly changes and adapts to the specific needs of the cell. One part of the cytoskeleton is a dense, flexible meshwork of fibers called the cortex that lies just beneath the surface of the cell. The cortex is constructed using a protein called actin, and many of these proteins join together to form each fiber. When cells need to adapt rapidly to an injury or other sudden changes in their environment they activate a so-called stress response. This response often begins with a rapid increase in the amount of calcium ions inside a cell, which can then trigger changes in actin organization. However, it is not clear how cells under stress are able to globally remodel their actin cytoskeleton without compromising stability and integrity of the cortex. Wales, Schuberth, Aufschnaiter et al. used a range of mammalian cells to investigate how actin responds to stress signals. All cells responded to the resulting influx of calcium ions by deconstructing large parts of the actin cortex and simultaneously forming actin filaments near the center of the cell. Wales, Schuberth, Aufschnaiter et al. termed this response calcium-mediated actin reset (CaAR), as it lasted for only a few minutes before the actin cortex reformed. The experiments show that a protein called INF2 controls CaAR by rapidly removing actin from the cortex and forming new filaments near a cell compartment called the endoplasmic reticulum. CaAR allows cells to rapidly and drastically alter the cortex in response to stress. The experiments also show that this sudden shift in actin can change the activity of certain genes, leading to longer-term effects on the cell. The findings of Wales, Schuberth, Aufschnaiter et al. suggest that calcium ions globally regulate the actin cytoskeleton and hence cell shape and movement under stress. This could be relevant for many important processes and conditions such as wound healing, inflammation and cancer. A future challenge will be to understand the role of CaAR in these processes. DOI: http://dx.doi.org/10.7554/eLife.19850.002