An optogenetic tool for the activation of endogenous diaphanous‐related formins induces thickening of stress fibers without an increase in contractility

Rao, Megha Vaman; Chu, Pei Hsuan; Hahn, Klaus M.; Zaidel-Bar, Ronen

doi:10.1002/cm.21115

Cited by 37 publications

(34 citation statements)

References 57 publications

(73 reference statements)

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“…This observation suggests compressive elastic stresses would increase the cofilin-mediated actin disassembly rate, consistent with our results. Molecules that mediate actin filament assembly are also candidate sensors such as formin proteins, which assemble actin and may play a role in remodeling SFs (32). Formins Dia1 and Bni1p showed ∼50% increased assembly rates per applied tensile force of 1 pN (33,34), suggesting the compressive stresses we estimate in SFs may have a substantial effect.…”

Section: Discussionmentioning

confidence: 87%

A mechanical-biochemical feedback loop regulates remodeling in the actin cytoskeleton

Stachowiak¹,

Smith

Blankman

et al. 2014

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

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Cytoskeletal actin assemblies transmit mechanical stresses that molecular sensors transduce into biochemical signals to trigger cytoskeletal remodeling and other downstream events. How mechanical and biochemical signaling cooperate to orchestrate complex remodeling tasks has not been elucidated. Here, we studied remodeling of contractile actomyosin stress fibers. When fibers spontaneously fractured, they recoiled and disassembled actin synchronously. The disassembly rate was accelerated more than twofold above the resting value, but only when contraction increased the actin density to a threshold value following a time delay. A mathematical model explained this as originating in the increased overlap of actin filaments produced by myosin II-driven contraction. Above a threshold overlap, this mechanical signal is transduced into accelerated disassembly by a mechanism that may sense overlap directly or through associated elastic stresses. This biochemical response lowers the actin density, overlap, and stresses. The model showed that this feedback mechanism, together with rapid stress transmission along the actin bundle, spatiotemporally synchronizes actin disassembly and fiber contraction. Similar actin remodeling kinetics occurred in expanding or contracting intact stress fibers but over much longer timescales. The model accurately described these kinetics, with an almost identical value of the threshold overlap that accelerates disassembly. Finally, we measured resting stress fibers, for which the model predicts constant actin overlap that balances disassembly and assembly. The overlap was indeed regulated, with a value close to that predicted. Our results suggest that coordinated mechanical and biochemical signaling enables extended actomyosin assemblies to adapt dynamically to the mechanical stresses they convey and direct their own remodeling.echanical signaling plays critical roles in diverse cellular processes such as cell migration, adhesion, differentiation, morphogenesis, and gene transcription (1-3). In these contexts, cytoskeletal actin structures spatially distribute mechanical stresses, thereby rapidly communicating mechanical information to remote locations within the cell (4). Transduction of this information to altered biochemical activity of local molecular mechanosensors can then activate remodeling of the cytoskeleton and other downstream events (2, 3). Mixed signaling pathways of this type involving either stress or strain sensors have been identified. The cytoskeleton conveys stresses that alter the binding activity of talin to vinculin in focal adhesions (5), and mechanical strains in actin networks in vitro were transduced by filamin cross-linkers into altered binding affinities for proteins that regulate downstream actin remodeling (6). However, it remains unclear how mechanical and biochemical signaling are coordinated in vivo to orchestrate complex cell-scale reorganizations of the cytoskeleton.Far from passive, actomyosin assemblies that convey mechanical stress are active and dynamic ...

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Section: Discussionmentioning

confidence: 87%

A mechanical-biochemical feedback loop regulates remodeling in the actin cytoskeleton

Stachowiak¹,

Smith

Blankman

et al. 2014

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

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“…1e). This technique has been used in conjunction with LOV domains to regulate CDC42 and RAC 14 , and formins 46 in the context of cell migration, in association with degrons to regulate protein degradation 47 and in conjunction with Dronpa to regulate CDC42 and proteinase K 19 . The advantage of this approach is that it only requires the expression of one protein.…”

Section: Optogenetic Control Of Cell Signallingmentioning

confidence: 99%

Illuminating cell signalling with optogenetic tools

Tischer

Weiner

2014

Nat Rev Mol Cell Biol

317

282

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The light-based control of ion channels has been transformative for the neurosciences, but the optogenetic toolkit does not stop there. An expanding number of proteins and cellular functions have been shown to be controlled by light, and the practical considerations in deciding between reversible optogenetic systems (such as systems that use light-oxygen-voltage domains, phytochrome proteins, cryptochrome proteins and the fluorescent protein Dronpa) are well defined. The field is moving beyond proof of concept to answering real biological questions, such as how cell signalling is regulated in space and time, that were difficult or impossible to address with previous tools.

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“…Moreover, light-mediated control of PI3K localization, by enabling the manipulation of PIP 3 levels 17, 50, might give insight into the requirement of this lipid for establishing and maintaining front/rear polarity. Finally, to gain a comprehensive understanding of cell polarity during migration, these tools could be complemented with other optogenetic systems to control organelle transport [38], activate proteins that promote actin polymerization such as diaphanous-related formins [51], and modulate the subcellular localization of specific polarity proteins [30].…”

Section: Optogenetic Modulation Of Molecular and Cellular Processes Dmentioning

confidence: 99%

Optogenetic Control of Protein Function: From Intracellular Processes to Tissue Morphogenesis

Guglielmi

Falk

Renzis

2016

Trends in Cell Biology

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Optogenetics is an emerging and powerful technique that allows the control of protein activity with light. The possibility of inhibiting or stimulating protein activity with the spatial and temporal precision of a pulse of laser light is opening new frontiers for the investigation of developmental pathways and cell biological bases underlying organismal development. With this powerful technique in hand, it will be possible to address old and novel questions about how cells, tissues, and organisms form. In this review, we focus on the applications of existing optogenetic tools for addressing issues in animal morphogenesis.

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An optogenetic tool for the activation of endogenous diaphanous‐related formins induces thickening of stress fibers without an increase in contractility

Cited by 37 publications

References 57 publications

A mechanical-biochemical feedback loop regulates remodeling in the actin cytoskeleton

A mechanical-biochemical feedback loop regulates remodeling in the actin cytoskeleton

Illuminating cell signalling with optogenetic tools

Optogenetic Control of Protein Function: From Intracellular Processes to Tissue Morphogenesis

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