Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Bolado-Carrancio, Alfonso; Rukhlenko, Oleksii S.; Nikonova, Elena; Tsyganov, M. A.; Wheeler, Anne; Munoz, Amaya Garcia; Kölch, Walter; Kriegsheim, Alex von; Kholodenko, Boris N.

doi:10.1101/2020.03.09.984054

Cited by 14 publications

(19 citation statements)

References 83 publications

(119 reference statements)

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“…It has been confirmed that Rho family (Cdc42, Rac1, and RhoA), which bind with IQGAP1, are also fundamental regulators of cell migration. [29][30][31] In addition, previous research shows that Rho family and IQGAP1 combine with F-actin to regulate microfilament remodeling. 32 Therefore, we further investigated whether Rho family are involved in IQGAP1-mediated BMSC migration.…”

Section: Iqgap1 Is Essential To S1p-induced Motility Of Bmscsmentioning

confidence: 99%

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Chang

Liu

et al. 2022

Molecular Therapy - Nucleic Acids

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IQ motif-containing guanosine triphosphatase (GTPase)-activating protein 1 (IQGAP1) is a cytosolic scaffolding protein involved in cell migration. Our previous studies suggest sphingosine 1-phosphate (S1P) triggers bone marrow (BM) mesenchymal stromal cells (BMSCs) to damaged liver, thereby promoting liver fibrosis. However, the role of IQGAP1 in S1Pinduced BMSC migration and liver fibrogenesis remains unclear. Chimeric mice of BM cell labeled by EGFP were used to build methionine-choline-deficient and high-fat (MCDHF)-dietinduced mouse liver fibrosis. IQGAP1 small interfering RNA (siRNA) was utilized to silence IQGAP1 in vivo. IQGAP1 expression is significantly elevated in MCDHF-diet-induced mouse fibrotic livers. Positive correlations are presented between IQ-GAP1 and fibrosis hallmarks expressions in human and mouse fibrotic livers. In vitro, depressing IQGAP1 expression blocks S1P-induced motility and cytoskeleton remodeling of BMSCs. S1P facilitates IQGAP1 aggregating to plasma membrane via S1P receptor 3 (S1PR 3 ) and Cdc42/Rac1. In addition, IQGAP1 binds to Cdc42/Rac1, regulating S1P-induced activation of Cdc42/Rac1 and mediating BMSC migration in concert. In vivo, silencing IQGAP1 reduces the recruitment of BMSCs to impaired liver and effectively alleviates liver fibrosis induced by MCDHF diet. Together, silencing IQGAP1 relieves liver fibrosis by blocking BMSC migration, providing an effective therapeutic strategy for liver fibrosis.

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Section: Iqgap1 Is Essential To S1p-induced Motility Of Bmscsmentioning

confidence: 99%

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Chang

Liu

et al. 2022

Molecular Therapy - Nucleic Acids

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“…We found that the protein FBP17 appeared in the phyla Chordata and Arthropoda according to GenBank database, and the exact sequence of the IDR of human FBP17L was found in the clade Amniota comprising the reptiles, birds, and mammals (see Transparent Methods). To see the sequence conservation, we generated the sequence logo (Crooks et al, 2004) from all FBP17 sequences ( Figure 3C). At each position, the overall height (entropy) depicted the information content (in bits) indicative of the sequence conservation, whereas the width (weight) was proportional to the fraction of existence.…”

Section: Two Isoforms Of Fbp17 Differ In Their Phases Of Recruitment mentioning

confidence: 99%

“…In addition, the IDR of the cytokinetic F-BAR protein Cdc15 in fission yeast was shown to be important for the maintenance of cytokinetic ring (Mangione et al, 2019). Cell protrusions and leading edge dynamics as well as cytokinesis are often simplified as actin cytoskeletal rearrangement but they are also controlled by cortical propagating waves and interlinked oscillatory networks (Bement et al, 2015;Bolado-Carrancio et al, 2020;Katsuno et al, 2015;Miao et al, 2017;Ruthel and Banker, 1999;Xiao et al, 2017). An intriguing possibility is that kinetic parameter changes could have implications in the conversion between regimes of dynamical systems (also known as bifurcations), which then result in morphogenetic outcomes.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Comparative Study of Curvature Sensing Mediated by F-BAR and an Intrinsically Disordered Region of FBP17

Zhuang

Miao

et al. 2020

iScience

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Membrane curvature has emerged as an intriguing physical principle underlying biological signaling and membrane trafficking. The CIP4/FBP17/Toca-1 F-BAR subfamily is unique in the BAR family because its structurally folded F-BAR domain does not contain any hydrophobic motifs that insert into membrane. Although widely assumed so, whether the banana-shaped F-BAR domain alone can sense curvature has never been experimentally demonstrated. Using a nanobar-supported lipid bilayer system, we found that the F-BAR domain of FBP17 displayed minimal curvature sensing in vitro. In comparison, an alternatively spliced intrinsically disordered region (IDR) adjacent to the F-BAR domain has the membrane curvature-sensing ability greatly exceeding that of F-BAR domain alone. In living cells, the presence of the IDR delayed the recruitment of FBP17 in curvature-coupled cortical waves. Collectively, we propose that contrary to the common belief, FBP17's curvature-sensing capability largely originates from IDR, and not the F-BAR domain alone.

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“…The mathematical tools presented here can be applied to analyse model systems of this nature. See for example [2,21,22,31].…”

Section: Conclusion and Discussionmentioning

confidence: 99%

A mathematical analysis of an activator-inhibitor Rho GTPase model

Juma

Dehmelt

Portet

et al. 2022

JCD

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<p style='text-indent:20px;'>Recent experimental observations reveal that local cellular contraction pulses emerge via a combination of fast positive and slow negative feedbacks based on a signal network composed of Rho, GEF and Myosin interactions [<xref ref-type="bibr" rid="b22">22</xref>]. As an examplary, we propose to study a plausible, hypothetical temporal model that mirrors general principles of fast positive and slow negative feedback, a hallmark for activator-inhibitor models. The methodology involves (ⅰ) a qualitative analysis to unravel system switching between different states (stable, excitable, oscillatory and bistable) through model parameter variations; (ⅱ) a numerical bifurcation analysis using the positive feedback mediator concentration as a bifurcation parameter, (ⅲ) a sensitivity analysis to quantify the effect of parameter uncertainty on the model output for different dynamic regimes of the model system; and (ⅳ) numerical simulations of the model system for model predictions. Our methodological approach supports the role of mathematical and computational models in unravelling mechanisms for molecular and developmental processes and provides tools for analysis of temporal models of this nature.</p>

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Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Cited by 14 publications

References 83 publications

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Comparative Study of Curvature Sensing Mediated by F-BAR and an Intrinsically Disordered Region of FBP17

A mathematical analysis of an activator-inhibitor Rho GTPase model

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