<i>Dictyostelium</i> chemotaxis: essential Ras activation and accessory signalling pathways for amplification

Kortholt, Arjan; Kataria, Rama; Keizer‐Gunnink, Ineke; Egmond, Wouter N. van; Khanna, Ankita; Haastert, Peter J.M. van

doi:10.1038/embor.2011.210

Cited by 55 publications

(112 citation statements)

References 29 publications

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“…Previous studies reported that disruption of four pathways (PI3K, TORC2, PLA 2 , and sGC) simultaneously abolishes chemotactic responses (10,11). In our hands, these cells were able to recruit LimE Δcoil following a brief pulse of flow, although the response was significantly reduced compared with cells lacking one (sGC) or two (sGC and PI3K) pathways (Fig.…”

Section: Role Of the Signal Transduction Network In The Response To Amentioning

confidence: 38%

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Artemenko

Axiotakis

Borleis

et al. 2016

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

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Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduction network, as well as actin polymerization. Similarly to chemoattractants, the shear flow-induced signal transduction events displayed features of excitability, including the ability to mount a full response irrespective of the length of the stimulation and a refractory period that is shared with that generated by chemoattractants. Loss of G protein subunits, inhibition of multiple signal transduction events, or disruption of calcium signaling attenuated the response to acute mechanical stimulation. Unlike the response to chemoattractants, an intact actin cytoskeleton was essential for reacting to mechanical perturbation. These results taken together suggest that chemotactic and mechanical stimuli trigger activation of a common signal transduction network that integrates external cues to regulate cytoskeletal activity and drive cell migration.biochemical excitability | shear stress | motility | biomechanics | inflammation

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Section: Role Of the Signal Transduction Network In The Response To Amentioning

confidence: 38%

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Artemenko

Axiotakis

Borleis

et al. 2016

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

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“…Four signaling enzymes, PI3K, TorC2, PLA2 and sGC, have been implicated in chemotaxis (Chen et al, 2007;Kamimura et al, 2008;Liao et al, 2010;. Cells lacking all four enzyme activities show normal Ras activation in cAMP gradients, but can only exhibit chemotaxis in steep cAMP gradients (Kortholt et al, 2011). These observations suggest that symmetry breaking during chemotaxis occurs at the level of Ras activation, and that activation of downstream signaling pathways is not essential for Ras activation and chemotaxis.…”

Section: Introductionmentioning

confidence: 66%

“…In Dictyostelium, a shallow gradient of cAMP induces the activation of cAMP receptors and the associated heterotrimeric G-protein Ga2bc in a manner that is approximately proportional to the steepness of the gradient (Elzie et al, 2009;Jin et al, 2000;Xiao et al, 1997). In contrast, activation of Ras is much stronger in the front than in the rear of chemotaxing cells (Charest et al, 2010;Kortholt et al, 2011;Sasaki et al, 2004;Sasaki and Firtel, 2006;Zhang et al, 2008). Several studies have shown that inactivation of both rasC and rasG results in defective cAMP-mediated chemotaxis (Bolourani et al, 2006;Kortholt et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, activation of Ras is much stronger in the front than in the rear of chemotaxing cells (Charest et al, 2010;Kortholt et al, 2011;Sasaki et al, 2004;Sasaki and Firtel, 2006;Zhang et al, 2008). Several studies have shown that inactivation of both rasC and rasG results in defective cAMP-mediated chemotaxis (Bolourani et al, 2006;Kortholt et al, 2011). Four signaling enzymes, PI3K, TorC2, PLA2 and sGC, have been implicated in chemotaxis (Chen et al, 2007;Kamimura et al, 2008;Liao et al, 2010;.…”

Section: Introductionmentioning

confidence: 99%

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Ras activation and symmetry breaking duringDictyosteliumchemotaxis

Kortholt

Keizer‐Gunnink

Kataria

et al. 2013

Journal of Cell Science

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SummaryCentral to chemotaxis is the molecular mechanism by which a shallow spatial gradient of chemoattractant induces symmetry breaking of activated signaling molecules. Previously, we have used Dictyostelium mutants to investigate the minimal requirements for chemotaxis, and identified a basal signaling module providing activation of Ras and F-actin at the leading edge. Here, we show that Ras activation after application of a pipette releasing the chemoattractant cAMP has three phases, each depending on specific guanine-nucleotideexchange factors (GEFs). Initially a transient activation of Ras occurs at the entire cell boundary, which is proportional to the local cAMP concentrations and therefore slightly stronger at the front than in the rear of the cell. This transient Ras activation is present in ga2 (gpbB)-null cells but not in gb (gpbA)-null cells, suggesting that Gbc mediates the initial activation of Ras. The second phase is symmetry breaking: Ras is activated only at the side of the cell closest to the pipette. Symmetry breaking absolutely requires Ga2 and Gbc, but not the cytoskeleton or four cAMP-induced signaling pathways, those dependent on phosphatidylinositol (3,4,5)-triphosphate [PtdIns(3,4,5)P 3 ], cGMP, TorC2 and PLA2. As cells move in the gradient, the crescent of activated Ras in the front half of the cell becomes confined to a small area at the utmost front of the cell. Confinement of Ras activation leads to cell polarization, and depends on cGMP formation, myosin and F-actin. The experiments show that activation, symmetry breaking and confinement of Ras during Dictyostelium chemotaxis uses different G-protein subunits and a multitude of Ras GEFs and GTPase-activating proteins (GAPs).

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“…Although the RasG activation was shown to occur independently of PI3K and actin polymerization, it has been proposed the presence of a positive feedback loop between RasG, PI3K and F-actin polymerization resulting in the amplification of the signal (Sasaki, A. et al 2004). The accumulation of PIP 3 serves as docking sites for many Pleckstrin homology (PH) domain-containing proteins, such as PKBA, that are important for cell polarity, cAMP relay and directional motility (Kae, H. et al 2004;Sasaki, A. et al 2006;Cai, H. and Devreotes, P. 2011;Kortholt, A. et al 2011). …”

Section: The Family Of Small Gtpases Ras Regulates Leading Edge Formamentioning

confidence: 99%

Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum

Rodriguez¹

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Dictyostelium chemotaxis: essential Ras activation and accessory signalling pathways for amplification

Cited by 55 publications

References 29 publications

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Ras activation and symmetry breaking duringDictyosteliumchemotaxis

Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum

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