An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns

Graessl, Melanie; Koch, Johannes; Calderon, Abram; Kamps, Dominic; Banerjee, Soumya; Mazel, Tomáš; Schulze, Nina; Jungkurth, Jana Kathrin; Patwardhan, Rutuja; Solouk, Djamschid; Hampe, Nico; Hoffmann, Bernd; Dehmelt, Leif; Nalbant, Perihan

doi:10.1083/jcb.201706052

Cited by 104 publications

(191 citation statements)

References 61 publications

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“…Alternatively, dynamic clustering of F-actin and/or Myosin II by scaffolding proteins such as Anillin could promote Myosin II recruitment and focal contraction (Maddox et al, 2005). Finally, autocatalytic activation of upstream regulators such as RhoA could drive local excitation, independent of, or in addition to, myosin-based tension or network contraction (Zhang and Glotzer, 2015;Munjal et al, 2015;Bement et al, 2015;Graessl et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, multiple forms of delayed negative feedback could contribute to terminating pulses, including progressive buildup of steric or elastic resistance to further contraction (Dierkes et al, 2014), or contraction-mediated disassembly, or delayed recruitment of disassembly factors or inhibitors of Myosin II or RhoA (Munjal et al, 2015;Kasza and Zallen, 2011;Bement et al, 2015;Graessl et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Excitable RhoA dynamics drive pulsed contractions in the earlyC. elegansembryo

Robin

McFadden

Munro

2016

Preprint

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Pulsed actomyosin contractility underlies diverse modes of tissue morphogenesis, but the underlying mechanisms remain poorly understood. Here, we combine quantitative imaging with genetic perturbations to identify a core mechanism for pulsed contractility in early C. elegans embryos. We show that pulsed accumulation of actomyosin is governed by local control of assembly and disassembly downstream of RhoA. Pulsed activation and inactivation of RhoA precede, respectively, accumulation and disappearance of actomyosin, and persist in the nearly complete absence of Myosin II.We find that fast positive feedback on RhoA activation drives pulse initiation, while Factin dependent accumulation of the RhoA GTPase activating proteins (GAPs) RGA-3/4 provides delayed negative feedback to terminate each pulse. An experimentally constrained mathematical model confirms that in principle these feedbacks are sufficient to generate locally excitable RhoA dynamics. We propose that excitable RhoA dynamics are a common driver for pulsed contractility that can be differently tuned or coupled to actomyosin dynamics to produce a diversity of morphogenetic outcomes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Excitable RhoA dynamics drive pulsed contractions in the earlyC. elegansembryo

Robin

McFadden

Munro

2016

Preprint

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“…38 Finally, in a very recent study, a glimpse is offered into the dynamics of local changes of Rho and Rho-target activity via temporal shift of recruitment of GEF-H1 (ARHGEF2) and the RhoGAP Myo9b. 39 …”

Section: Are Gaps Lonely Players?mentioning

confidence: 99%

The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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Background: GTPase-activating proteins (GAPs) accelerate the rate of hydrolysis of GTP bound to small GTPases, thereby limiting the prevalence and concentration of the active, GTP-bound form of these proteins. The large number of potential GAPs acting on members of the Rho family of small GTPases raises the question of specificity or redundancy. Results: In this review, we summarize experimental data obtained on the role of Rho family GAPs in neutrophils, highlight cases where more than one GAP is involved in a physiological function and show examples that GAPs can be involved not only in termination but also in initiation of cellular processes. We demonstrate that the expression-level regulation of GAPs may also occur in shortliving cells such as neutrophils. Finally, we provide insight into the existence and structure of molecular complexes in which Rho family GAPs are involved. Conclusion: GAPs play more complex and varied roles than being simple terminators of cellular processes. K E Y W O R D SGTPase activating proteins, Rho-family small GTPases, neutrophils

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“…Robin et al (2016) (Robin et al, 2016) followed spikes of actin nucleation and disassembly during pulsed contractility of the early C. elegans embryo, and identified two RhoGAP proteins that are recruited to the sites of actin nucleation and keep the cell surface plastic. An analogous circuitry was recently shown to regulate cell contractility in cell culture (Graessl et al, 2017). In this case, the actin nucleation and disassembly cascade was coupled to the activity of Myosin II, which may allow spontaneous patterns of subcellular contractility to explore local mechanical cues.…”

Section: Discussionmentioning

confidence: 94%

Formation and disassembly of a contractile actomyosin network mediates content release from large secretory vesicles

Segal

Zaritsky

Schejter

et al. 2017

Preprint

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SummaryThis work identified a cycle of actin assembly and disassembly in large secretory vesicles of Drosophila salivary glands. Actin disassembly is triggered by actindependent recruitment of a RhoGAP protein, and is essential for the contractility of the vesicle leading to content release to the lumen. AbstractSecretion of adhesive glycoproteins to the lumen of Drosophila larval salivary glands is carried out by contraction of an actomyosin network that is assembled around large secretory vesicles, following their fusion to the apical membranes. We have identified a cycle of actin coat nucleation and disassembly that is independent of myosin.Recruitment of active Rho1 to the fused vesicle triggers activation of the formin Diaphanous and nucleation of linear actin. This, in turn, leads to actin-dependent localization of a RhoGAP protein that locally shuts off Rho1, promoting disassembly of the actin coat. Recruitment of the branched actin nucleation machinery is also required for effective Rho1 inactivation. Interestingly, different blocks to actin coat disassembly arrested vesicle contraction, indicating that actin turnover is an integral part of the actomyosin contraction cycle. The capacity of F-actin to trigger a negative feedback on its own production may be utilized in a variety of scenarios, to coordinate a succession of morphogenetic events or maintain homeostasis.

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An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns

Abstract: A signaling network is revealed that combines positive and negative feedback to control the activity of the small GTPase Rho in adherent cells. This network generates spontaneous pulses of Rho activity and actomyosin contraction that are modulated by extracellular elasticity.

Cited by 104 publications

References 61 publications

Excitable RhoA dynamics drive pulsed contractions in the earlyC. elegansembryo

Excitable RhoA dynamics drive pulsed contractions in the earlyC. elegansembryo

The neglected terminators: Rho family GAPs in neutrophils

Formation and disassembly of a contractile actomyosin network mediates content release from large secretory vesicles

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