Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

Abstract

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

Inverted formins: A subfamily of atypical formins

“…CaAR initiates with a spike of intracellular calcium, which is immediately followed by polymerization of an “actin ridge” around the nucleus, loss of cortical actin but stiffening of the subcortical region, freezing of organelles, and changes in gene expression through myocardin-related transcription factors [Shao et al, 2015; Wales et al, 2016]. Polymerization of the actin ridge is INF2 dependent, and can stimulated by either the CAAX or non-CAAX isoform; for cells in which INF2 has been knocked down, neither polymerization nor other downstream effects occur [Shao et al, 2015; Wales et al, 2016]. While INF2 does not have a known calcium-sensing domain, Wales and colleagues demonstrated that in the presence of calcium, calmodulin binds INF2, pointing to a possible mechanism of activation [Wales et al, 2016].…”

“…Polymerization of the actin ridge is INF2 dependent, and can stimulated by either the CAAX or non-CAAX isoform; for cells in which INF2 has been knocked down, neither polymerization nor other downstream effects occur [Shao et al, 2015; Wales et al, 2016]. While INF2 does not have a known calcium-sensing domain, Wales and colleagues demonstrated that in the presence of calcium, calmodulin binds INF2, pointing to a possible mechanism of activation [Wales et al, 2016]. …”

“…loss of cortical actin but stiffening of the subcortical region, freezing of organelles, and changes in gene expression through myocardin-related transcription factors(Shao, Mogilner, Bershadsky, & Shivashankar, 2015;Wales et al, 2016). Polymerization of the actin ridge is INF2 dependent, and can be stimulated by either the CAAX or non-CAAX isoform; for cells in which INF2 has been knocked down, neither polymerization nor other downstream effects occur(Shao et al, 2015;Wales et al, 2016).…”

“…loss of cortical actin but stiffening of the subcortical region, freezing of organelles, and changes in gene expression through myocardin-related transcription factors(Shao, Mogilner, Bershadsky, & Shivashankar, 2015;Wales et al, 2016). Polymerization of the actin ridge is INF2 dependent, and can be stimulated by either the CAAX or non-CAAX isoform; for cells in which INF2 has been knocked down, neither polymerization nor other downstream effects occur(Shao et al, 2015;Wales et al, 2016). While INF2 does not have a known calciumsensing domain, Wales and colleagues demonstrated that in the presence of calcium, calmodulin binds INF2, pointing to a possible mechanism of activation(Wales et al, 2016).What remains a challenge is correlating the various effects of INF2on actin dynamics in vitro with its ability to promote actin organization in vivo.…”

Cellular mechanisms and signals that coordinate plasma membrane repair

“…Actin response to plasma membrane injury is biphasic, with initial depolymerization being followed by accumulation at the site of injury [148]. Cortical actin disassembly and reassembly in response to calcium increase occurs immediately after injury and is mediated by the formin INF2 [150]. Loss of cortical actin relieves membrane tension preventing the damaged free edges of the wound site from expanding outward and provides physical space to allow vesicles to fuse with the plasma membrane [14,62].…”