Coupled excitable Ras and F-actin activation mediates spontaneous pseudopod formation and directed cell movement

Haastert, Peter J.M. van; Keizer‐Gunnink, Ineke; Kortholt, Arjan

doi:10.1091/mbc.e16-10-0733

Cited by 65 publications

(139 citation statements)

References 56 publications

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“…Especially microtubules are discussed as important in this respect [157] [140] [141] [142], representing quantum channels related to consciousness [158] [159] and terahertz oscillations in tubulin were reported to be affected by exposures to anesthetics [160]. Besides microtubules, also the actin filaments behave as excitable medium which transports ionic waves and mediates eukaryotic chemotaxis in response to diverse gradients [161] [162] [163] [164]. Actin cytoskeleton supports lipid rafts, which are ordered domains of biological membranes particularly sensitive to anesthetics [165] [166] [167] [168].…”

Section: Emerging Sources Of Cellular Levels Of Sentience and Consciomentioning

confidence: 99%

Slime mould: The fundamental mechanisms of biological cognition

et al. 2018

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The slime mould Physarum polycephalum has been used in developing unconventional computing devices for in which the slime mould played a role of a sensing, actuating, and computing device. These devices treated the slime mould as an active living substrate, yet it is a self-consistent living creature which evolved over millions of years and occupied most parts of the world, but in any case, that living entity did not own true cognition, just automated biochemical mechanisms. To "rehabilitate" slime mould from the rank of a purely living electronics element to a "creature of thoughts" we are analyzing the cognitive potential of P. polycephalum. We base our theory of minimal cognition of the slime mould on a bottom-up approach, from the biological and biophysical nature of the slime mould and its regulatory systems using frameworks such as Lyon's biogenic cognition, Muller, di Primio-Lengelerś modifiable pathways, Bateson's "patterns that connect" framework, Maturana's autopoietic network, or proto-consciousness and Morgan's Canon.

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Section: Emerging Sources Of Cellular Levels Of Sentience and Consciomentioning

confidence: 99%

Slime mould: The fundamental mechanisms of biological cognition

et al. 2018

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“…We found that Ras/Rap‐ and Rac/actin‐centered networks, STEN and CEN, respectively, interact to control dynamic wave patterns at the cell cortex. Although the components we highlight are only a subset of the overall system (Devreotes et al , ; van Haastert et al , ; Fort et al , ; Li et al , ; Tanabe et al , ), they capture essential features of wave organization. In each network, various components sequentially and coordinately engage in wave propagation.…”

Section: Discussionmentioning

confidence: 99%

Wave patterns organize cellular protrusions and control cortical dynamics

Miao

Bhattacharya

Banerjee

et al. 2019

Molecular Systems Biology

175

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Cellular protrusions are typically considered as distinct structures associated with specific regulators. However, we found that these regulators coordinately localize as propagating cortical waves, suggesting a common underlying mechanism. These molecular events fell into two excitable networks, the signal transduction network STEN and the cytoskeletal network CEN with different wave substructures. Computational studies using a coupled‐network model reproduced these features and showed that the morphology and kinetics of the waves depended on strengths of feedback loops. Chemically induced dimerization at multiple nodes produced distinct, coordinated alterations in patterns of other network components. Taken together, these studies indicate: STEN positive feedback is mediated by mutual inhibition between Ras/Rap and PIP 2, while negative feedback depends on delayed PKB activation; PKB s link STEN to CEN ; CEN includes positive feedback between Rac and F‐actin, and exerts fast positive and slow negative feedbacks to STEN . The alterations produced protrusions resembling filopodia, ruffles, pseudopodia, or lamellipodia, suggesting that these structures arise from a common regulatory mechanism and that the overall state of the STEN ‐ CEN system determines cellular morphology.

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“…“Actin waves” were first reported by Vicker in Dictyostelium (Vicker, 2002) and extensively characterized by Gerisch and colleagues (Bretschneider et al, 2004; Bretschneider et al, 2009; Gerisch et al, 2009; Gerisch, 2010; Gerisch et al, 2011; Schroth-Diez et al, 2009). Waves of the biosensors for Ras (Xiong et al, 2010) (van Haastert et al, 2017) and PI3K activation were also observed in cells during migration. Studies of the recruitment of Scar subunits, F-actin binding proteins, and biosensors for Ras, PI3K, and Rac activation and coordinated dissociation of PTEN and myosin from the cell cortex suggest that the entire signal transduction and cytoskeletal networks show this behavior (Supplemental Video 5)).…”

Section: The Signal Transduction “Excitable” Network or Stenmentioning

confidence: 94%

“…Different sensitivities among patches as well as individual cells feed into the dose-response behavior. More sensitive methods have detected smaller, perhaps subthreshold, patches Ras activity that do not expand (van Haastert et al, 2017). Third, refractory periods for chemoattractant and shear force-elicited PIP3 production were demonstrated by applying short, paired stimuli and monitoring the response to the second (Nishikawa et al, 2014; Huang et al, 2013; Artemenko et al, 2016).…”

Section: The Signal Transduction “Excitable” Network or Stenmentioning

confidence: 99%

Excitable Signal Transduction Networks in Directed Cell Migration

Devreotes

Bhattacharya

Edwards

et al. 2017

Annu. Rev. Cell Dev. Biol.

162

168

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While directed migration may have evolved to escape nutrient depletion, it has been adopted for an extensive range of physiological events during development and in the adult. The subversion of these movements results in disease. Though the mechanisms of propulsion and sensing are extremely diverse, most cells move by extending actin-filled protrusions called macropinosomes, pseudopodia, or lamellipodia or by extension of blebs. In addition to motility, directed migration involves polarity and directional sensing. The hundreds of gene products involved in these processes are organized into networks of parallel and interconnected pathways. Many of these components are activated or inhibited coordinately with stimulation and on each spontaneously extended protrusion. Moreover, these networks display hallmarks of excitability, including “all-or-nothing” responsiveness and wave propagation. Cellular protrusions result from signal transduction waves which propagate outwardly from an origin and drive cytoskeletal activity. The range of the propagating waves and hence the size of the protrusions can be altered by lowering or raising the threshold for network activation, with larger and wider protrusions favoring gliding or oscillatory behavior over amoeboid migration. Here, we evaluate the variety of models of excitable networks controlling directed migration and outline critical tests. We also discuss the utility of this emerging view in producing cell migration and in integrating the various extrinsic cues that direct migration.

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Coupled excitable Ras and F-actin activation mediates spontaneous pseudopod formation and directed cell movement

Cited by 65 publications

References 56 publications

Slime mould: The fundamental mechanisms of biological cognition

Slime mould: The fundamental mechanisms of biological cognition

Wave patterns organize cellular protrusions and control cortical dynamics

Excitable Signal Transduction Networks in Directed Cell Migration

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