Single cell pattern formation and transient cytoskeletal arrays

Dassow, George von

doi:10.1016/j.ceb.2013.09.005

Cited by 25 publications

(23 citation statements)

References 67 publications

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“…This suggests that an additional GEF-GAP signaling network shapes this specific subcellular Rac1 activation pattern through a reaction-diffusion system (Bement and von Dassow, 2014). The fact that srGAP2 colocalizes with active Rac1 during contact protrusion extension necessitates that its GAP activity is not constitutively active.…”

Section: Discussionmentioning

confidence: 98%

SrGAP2-Dependent Integration of Membrane Geometry and Slit-Robo-Repulsive Cues Regulates Fibroblast Contact Inhibition of Locomotion

et al. 2015

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Migrating fibroblasts undergo contact inhibition of locomotion (CIL), a process that was discovered five decades ago and still is not fully understood at the molecular level. We identify the Slit2-Robo4-srGAP2 signaling network as a key regulator of CIL in fibroblasts. CIL involves highly dynamic contact protrusions with a specialized actin cytoskeleton that stochastically explore cell-cell overlaps between colliding fibroblasts. A membrane curvature-sensing F-BAR domain pre-localizes srGAP2 to protruding edges and terminates their extension phase in response to cell collision. A FRET-based biosensor reveals that Rac1 activity is focused in a band at the tip of contact protrusions, in contrast to the broad activation gradient in contact-free protrusions. SrGAP2 specifically controls the duration of Rac1 activity in contact protrusions, but not in contact-free protrusions. We propose that srGAP2 integrates cell edge curvature and Slit-Robo-mediated repulsive cues to fine-tune Rac1 activation dynamics in contact protrusions to spatiotemporally coordinate CIL.

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Section: Discussionmentioning

confidence: 98%

SrGAP2-Dependent Integration of Membrane Geometry and Slit-Robo-Repulsive Cues Regulates Fibroblast Contact Inhibition of Locomotion

et al. 2015

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“…At the singlecell level, spatial patterns are readily apparent in the formation of protein gradients and the regular arrangement of cytoskeletal structures, macromolecular complexes, and organelles. Intracellular patterning serves important functions, as it provides a means for cells to organize their intracellular space, sense their geometry, and partition their cellular content (1)(2)(3)(4)(5). However, the mechanisms that drive intracellular patterning are often poorly understood.…”

mentioning

confidence: 99%

DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos

Surovtsev

Campos

Jacobs‐Wagner

2016

Proc. Natl. Acad. Sci. U.S.A.

121

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Spatial ordering of macromolecular components inside cells is important for cellular physiology and replication. In bacteria, ParA/B systems are known to generate various intracellular patterns that underlie the transport and partitioning of low-copy-number cargos such as plasmids. ParA/B systems consist of ParA, an ATPase that dimerizes and binds DNA upon ATP binding, and ParB, a protein that binds the cargo and stimulates ParA ATPase activity. Inside cells, ParA is asymmetrically distributed, forming a propagating wave that is followed by the ParB-rich cargo. These correlated dynamics lead to cargo oscillation or equidistant spacing over the nucleoid depending on whether the cargo is in single or multiple copies. Currently, there is no model that explains how these different spatial patterns arise and relate to each other. Here, we test a simple DNArelay model that has no imposed asymmetry and that only considers the ParA/ParB biochemistry and the known fluctuating and elastic dynamics of chromosomal loci. Stochastic simulations with experimentally derived parameters demonstrate that this model is sufficient to reproduce the signature patterns of ParA/B systems: the propagating ParA gradient correlated with the cargo dynamics, the single-cargo oscillatory motion, and the multicargo equidistant patterning. Stochasticity of ATP hydrolysis breaks the initial symmetry in ParA distribution, resulting in imbalance of elastic force acting on the cargo. Our results may apply beyond ParA/B systems as they reveal how a minimal system of two players, one binding to DNA and the other modulating this binding, can transform directionally random DNA fluctuations into directed motion and intracellular patterning. intracellular patterning | active transport | ParA/B system | partitioning | mathematical model S patial patterns are omnipresent in biology, spanning a wide range of size scales and organizational levels. At the singlecell level, spatial patterns are readily apparent in the formation of protein gradients and the regular arrangement of cytoskeletal structures, macromolecular complexes, and organelles. Intracellular patterning serves important functions, as it provides a means for cells to organize their intracellular space, sense their geometry, and partition their cellular content (1-5). However, the mechanisms that drive intracellular patterning are often poorly understood.In this study, we aimed to understand how spatial patterns driven by bacterial ParA/B systems can arise within a small (micrometer-scale) intracellular space dominated by fluctuations and diffusion. ParA/B systems consist of only two proteins, ParA and ParB, that drive the transport and equipartitioning of lowcopy-number macromolecular complexes, often referred to as cargos. ParA/B systems are widespread among bacteria (6). For example, many low-copy-number plasmids encode a ParA/B system that distributes plasmid copies at regular intervals along the cell length (7-10). This striking plasmid patterning ensures that division at midcell results in ...

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“…Our data strongly suggest that DLC1 is involved in the fine spatial regulation of the focused RhoA activation pool at the tip of F-actin bundles, which most likely involves reaction-diffusion systems as previously documented for RhoA (Bement and von Dassow, 2014). This specific spatiotemporal RhoA activity pool might serve to locally position the formin mDia1 to polymerize F-actin to enable filopodia extension (Goh et al, 2012).…”

Section: Discussionmentioning

confidence: 75%

Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

Fusco¹,

Lefort²,

Smith³

et al. 2016

J Exp Med

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Abbreviations used in this paper: CV, computer vision; FRET, Förster resonance energy transfer; GAP, GTPase-activating protein; GEF, guanine nucleotide-exchange factor; HDS, hierarchical data structure; HS, high stringency; KD, knockdown; LS, low stringency; MDS, morphodynamic signature; MLCK, myosin light chain kinase; MP, morphogenetic process; MRCK, myotonin-related dystrophyn kinase myosin light chain kinase; pMLC, myosin light chain phosphorylation.

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Single cell pattern formation and transient cytoskeletal arrays

Cited by 25 publications

References 67 publications

SrGAP2-Dependent Integration of Membrane Geometry and Slit-Robo-Repulsive Cues Regulates Fibroblast Contact Inhibition of Locomotion

SrGAP2-Dependent Integration of Membrane Geometry and Slit-Robo-Repulsive Cues Regulates Fibroblast Contact Inhibition of Locomotion

DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos

Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

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