Ras activation and symmetry breaking during<i>Dictyostelium</i>chemotaxis

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

doi:10.1242/jcs.132340

Cited by 48 publications

(90 citation statements)

References 60 publications

(95 reference statements)

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“…This would then allow directional migration to last for a limited period before inhibitory signals reach a level to overcome the excitation signals and cause a switch in direction. The existence of such buildup of inhibitory signals may involve either a delay or a slow rate in their generation following protrusion, as was suggested by a transient peak of various activities at the front, such as Ras, upon the stimulation of cell migration (54,55). On 2D surfaces, we would expect similar oscillations around the cell perimeter upon the disassembly of microtubules.…”

Section: Discussionmentioning

confidence: 80%

Microtubules stabilize cell polarity by localizing rear signals

Zhang

Guo

Wang

2014

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

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Microtubules are known to play an important role in cell polarity; however, the mechanism remains unclear. Using cells migrating persistently on micropatterned strips, we found that depolymerization of microtubules caused cells to change from persistent to oscillatory migration. Mathematical modeling in the context of a local-excitation–global-inhibition control mechanism indicated that this mechanism can account for microtubule-dependent oscillation, assuming that microtubules remove inhibitory signals from the front after a delayed generation. Experiments further supported model predictions that the period of oscillation positively correlates with cell length and that oscillation may be induced by inhibiting retrograde motors. We suggest that microtubules are required not for the generation but for the maintenance of cell polarity, by mediating the global distribution of inhibitory signals. Disassembly of microtubules induces cell oscillation by allowing inhibitory signals to accumulate at the front, which stops frontal protrusion and allows the polarity to reverse.

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Section: Discussionmentioning

confidence: 80%

Microtubules stabilize cell polarity by localizing rear signals

Zhang

Guo

Wang

2014

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

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“…Ras activation is an early response of the chemotaxis network and activated Ras localizes in patches at the front of the cell in a static gradient (33,34). Several experiments were also repeated with a downstream directionalsensing marker for phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ), PH-GFP (35,36).…”

Section: Resultsmentioning

confidence: 99%

Cellular memory in eukaryotic chemotaxis

Skoge

Yue

Erickstad

et al. 2014

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

131

176

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Natural chemical gradients to which cells respond chemotactically are often dynamic, with both spatial and temporal components. A primary example is the social amoeba Dictyostelium, which migrates to the source of traveling waves of chemoattractant as part of a self-organized aggregation process. Despite its physiological importance, little is known about how cells migrate directionally in response to traveling waves. The classic back-of-the-wave problem is how cells chemotax toward the wave source, even though the spatial gradient reverses direction in the back of the wave. Here, we address this problem by using microfluidics to expose cells to traveling waves of chemoattractant with varying periods. We find that cells exhibit memory and maintain directed motion toward the wave source in the back of the wave for the natural period of 6 min, but increasingly reverse direction for longer wave periods. Further insights into cellular memory are provided by experiments quantifying cell motion and localization of a directional-sensing marker after rapid gradient switches. The results can be explained by a model that couples adaptive directional sensing to bistable cellular memory. Our study shows how spatiotemporal cues can guide cell migration over large distances.cell motility | directional sensing | polarity | cell signaling E ukaryotic chemotaxis-the directed motion of cells along spatial gradients of chemicals-plays an essential role in a wide variety of biological processes, including embryogenesis, neuronal patterning, wound healing, and tumor dissemination (1-5), and many of its molecular components are conserved across cell types (6, 7). Much work has been devoted to understanding chemotaxis in static gradients (8, 9) and has revealed that cells are highly sensitive to spatial cues (10, 11). Natural chemical gradients, however, are often dynamic (12, 13), and chemotaxis in such environments requires an integration of spatial and temporal cues which is poorly understood. One striking example is the self-organized chemoattractant field arising during the development of the social amoeba Dictyostelium following nutrient deprivation. Here, nondissipating waves of chemoattractant travel outward from aggregation centers and provide stable long-range cues to direct the migration of cells toward the wave source. In a symmetric traveling wave, the spatial gradients in the front and back halves of the wave are equal in strength, but opposite in direction. Hence, if a cell responded simply to spatial information, it would move forward in the front of the wave and backward in the back of the wave. Thus, additional processing is needed for cells to solve the resulting back-of-the-wave problem (14) and to move efficiently toward the wave source.In principle, cells could distinguish between the front and back of the wave by the temporal gradient-the concentration increases in time in the front of the wave and decreases in time in the back of the wave. Temporal gradient sensing plays a fundamental role in bacterial chemotax...

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“…First, it has been shown that in strains deficient in cAMP signaling, such as the car1/3 – and gβ – strains, there is no chemoattractant-mediated Ras activation [53]. In gα2 – cells there is a brief, weak Ras activation [54]. Second, RasC and RasG proteins activate separate downstream pathways (Figure 3): RasC-GTP activates TORC2, whereas RasG-GTP and RasD-GTP interact with and activate PI3K1 and PI3K2 [47,55,56].…”

Section: Chemotactic Network Of Dictyostelium and Leukocytesmentioning

confidence: 99%

Moving towards a paradigm: common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes

Artemenko

Lampert

Devreotes

2014

Cell. Mol. Life Sci.

178

221

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Chemotaxis, or directed migration of cells along a chemical gradient, is a highly coordinated process that involves gradient sensing, motility, and polarity. Most of our understanding of chemotaxis comes from studies of cells undergoing amoeboid-type migration, in particular the social amoeba Dictyostelium discoideum and leukocytes. In these amoeboid cells the molecular events leading to directed migration can be conceptually divided into four interacting networks: receptor/G protein, signal transduction, cytoskeleton, and polarity. The signal transduction network occupies a central position in this scheme as it receives direct input from the receptor/G protein network, as well as feedback from the cytoskeletal and polarity networks. Multiple overlapping modules within the signal transduction network transmit the signals to the actin cytoskeleton network leading to biased pseudopod protrusion in the direction of the gradient. The overall architecture of the networks, as well as the individual signaling modules are remarkably conserved between Dictyostelium and mammalian leukocytes, and the similarities and differences between the two systems are the subject of this review.

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Ras activation and symmetry breaking duringDictyosteliumchemotaxis

Cited by 48 publications

References 60 publications

Microtubules stabilize cell polarity by localizing rear signals

Microtubules stabilize cell polarity by localizing rear signals

Cellular memory in eukaryotic chemotaxis

Moving towards a paradigm: common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes

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