scholarly journals Excitable dynamics of Ras triggers self-organized PIP3 signaling for spontaneous cell migration

2018 ◽  
Author(s):  
Seiya Fukushima ◽  
Satomi Matsuoka ◽  
Masahiro Ueda
Keyword(s):  
Symmetry Breaking ◽  
Cell Movement ◽  
Direct Interaction ◽  
Feedback Regulation ◽  
Asymmetric Distribution ◽  
Spatial Cues ◽  
Downstream Signaling ◽  
Self Organized ◽  
Ras Activation ◽  
Tightly Coupled

Spontaneous cell movement is underpinned by an asymmetric distribution of signaling molecules including small G proteins and phosphoinositides on the cell membrane. A fundamental question is the molecular mechanism for the spontaneous symmetry breaking. Here we report that GTP bound Ras (Ras-GTP) breaks the symmetry due to excitability even in the absence of extracellular spatial cues and cytoskeletal polarity as well as downstream signaling activities. A stochastic excitation of local and transient Ras activation induced PIP3 accumulation via direct interaction with PI3K, causing tightly coupled traveling waves propagating along the membrane. Comprehensive phase analysis of the waves of Ras-GTP and PIP3 metabolism-related molecules revealed the network structure of the excitable system including positive feedback regulation of Ras-GTP by PIP3. A mathematical model reconstituted a series of the observed symmetry breaking phenomena, illustrating an essential involvement of excitability in the cellular decision-making process.

Studies of Compositional Variations in Germanium Quantum Dots Grown on Silicon

2000 ◽  
Vol 638 ◽  
Author(s):  
Alan D.F. Dunbar ◽  
Matthew P. Halsall ◽  
Uschi Bangert ◽  
Alan Harvey ◽  
Philip Dawson ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Scanning Transmission Electron Microscopy ◽  
The Self ◽  
Asymmetric Distribution ◽  
Scanning Transmission Electron ◽  
Self Organized ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
The Uk

AbstractWe report optical and scanning transmission electron microscopy studies of germanium dots grown on silicon. In an attempt to control the self-organized growth process and promote dot size uniformity the dot layers were grown on a 4.5nm Si0.6Ge0.4 alloy template layer. Photoluminescence results indicate the formation of carrier confining Ge rich islands, whilst Raman scattering results indicate the presence of an alloy throughout the structures formed. The samples were studied in the UK high resolution scanning transmission electron microscopy facility at Liverpool, UK. Energy dispersive analysis of individual line scans through the sample show that the structures are composed of an alloy throughout with an asymmetric distribution of Germanium in the dots and in the wetting layer close to the dots. We discuss the results in the light of the proposed growth mode for these dots and conclude that attempts to manipulate the composition of these dots during growth may be problematic due to the self-organized nature of their formation.

The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium cells are not random

1993 ◽  
Vol 106 (4) ◽  
pp. 1005-1013 ◽  
Author(s):  
T. Killich ◽  
P.J. Plath ◽  
X. Wei ◽  
H. Bultmann ◽  
L. Rensing ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Actin Polymerization ◽  
Cell Movement ◽  
Time Lapse ◽  
Phase Resetting ◽  
Wave Interference ◽  
Self Organized ◽  
Classical Wave ◽  
Spatiotemporal Oscillations ◽  
Oscillatory Waves

The dynamic periphery of unstimulated, preaggregation, hunger-stage Dictyostelium discoideum amoebae was investigated by time-lapse videomicroscopy and digital image processing. Circular maps (i.e. of each of 360 radii around the cell transformed upon Cartesian coordinates) were constructed around the centroid of individual cell images and analysed in time series. This novel technique generated spatiotemporal structures of various degrees of order in the maps, which resemble classical wave interference patterns. The patterns thus demonstrate that cell movement is not random and that cells are intrinsically vibrating bodies, transited by self-organized, superpositioned, harmonic modes of rotating oscillatory waves (ROWS). These waves appear to depend upon spatiotemporal oscillations in the physicochemical reactions associated with actin polymerization, and they govern pseudopodial movements, cell shape and locomotion generally. ROWS in this case are unrelated to the cyclic-AMP-regulated oscillations, which characterize later, aggregative populations of Dictyostelium. However, the exposure of aggregation-stage cells to a pulse of the chemoattractant cyclic-AMP induces a characteristic sequence of changes in the global cellular concentration and spatiotemporal distribution of fibrillar (F-)actin. This reaction begins with what appears to be a phase resetting of ROWS and it may, therefore, underlie the cellular perception of and response to chemotactic signals. We also develop here an analytical mathematical description of ROWS, and use it to simulate cell movements accurately.

Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2440-2450 ◽  
Author(s):  
Itaru Matsumura ◽  
Akira Kawasaki ◽  
Hirokazu Tanaka ◽  
Junko Sonoyama ◽  
Sachiko Ezoe ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Cell Lines ◽  
Direct Interaction ◽  
Myeloid Cell ◽  
Megakaryocytic Differentiation ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Endogenous Expression ◽  
Ras Activation

Abstract Lineage-specific transcription factors play crucial roles in the development of hematopoietic cells. In a previous study, it was demonstrated that Ras activation was involved in thrombopoietin-induced megakaryocytic differentiation. In this study, constitutive Ras activation by H-rasG12V evoked megakaryocytic maturation of erythroleukemia cell lines F-36P and K562, but not of myeloid cell line 32D cl3 that lacks GATA-1. However, the introduction of GATA-1 led to reprogramming of 32D cl3 toward erythrocytic/megakaryocytic lineage and enabled it to undergo megakaryocytic differentiation in response to H-rasG12V. In contrast, the overexpression of PU.1 and c-Myb changed the phenotype of K562 from erythroid to myeloid/monocytic lineage and rendered K562 to differentiate into granulocytes and macrophages in response to H-rasG12V, respectively. In GATA-1–transfected 32D cl3, the endogenous expression of PU.1 and c-Myb was easily detectable, but their activities were reduced severely. Endogenous GATA-1 activities were markedly suppressed in PU.1-transfected and c-myb–transfected K562. As for the mechanisms of these reciprocal inhibitions, GATA-1 and PU.1 were found to associate through their DNA-binding domains and to inhibit the respective DNA-binding activities of each other. In addition, c-Myb bound to GATA-1 and inhibited its DNA-binding activities. Mutant GATA-1 and PU.1 that retained their own transcriptional activities but could not inhibit the reciprocal partner were less effective in changing the lineage phenotype of 32D cl3 and K562. These results suggested that GATA-1 activities may be crucial for Ras-mediated megakaryocytic differentiation and that its activities may be regulated by the direct interaction with other lineage-specific transcription factors such as PU.1 and c-Myb.

scholarly journals Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics

2018 ◽  
Vol 373 (1747) ◽  
pp. 20170145 ◽  
Author(s):  
Suvrajit Saha ◽  
Tamas L. Nagy ◽  
Orion D. Weiner
Keyword(s):  
Cell Biology ◽  
Cell Movement ◽  
Special Focus ◽  
Cellular Motility ◽  
Cellular Polarity ◽  
Self Organized ◽  
Cytoskeletal Dynamics ◽  
Physical Forces ◽  
Cytoskeletal Rearrangements

Dynamic processes like cell migration and morphogenesis emerge from the self-organized interaction between signalling and cytoskeletal rearrangements. How are these molecular to sub-cellular scale processes integrated to enable cell-wide responses? A growing body of recent studies suggest that forces generated by cytoskeletal dynamics and motor activity at the cellular or tissue scale can organize processes ranging from cell movement, polarity and division to the coordination of responses across fields of cells. To do so, forces not only act mechanically but also engage with biochemical signalling. Here, we review recent advances in our understanding of this dynamic crosstalk between biochemical signalling, self-organized cortical actomyosin dynamics and physical forces with a special focus on the role of membrane tension in integrating cellular motility. This article is part of the theme issue ‘Self-organization in cell biology’.

scholarly journals Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement

2004 ◽  
Vol 167 (3) ◽  
pp. 505-518 ◽  
Author(s):  
Atsuo T. Sasaki ◽  
Cheryl Chun ◽  
Kosuke Takeda ◽  
Richard A. Firtel
Keyword(s):  
Actin Polymerization ◽  
Cell Movement ◽  
Leading Edge ◽  
Ras Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Ras Activation ◽  
Directional Movement ◽  
Ras Effectors ◽  
Chemotaxis Receptors ◽  
Intermediate Event

During chemotaxis, receptors and heterotrimeric G-protein subunits are distributed and activated almost uniformly along the cell membrane, whereas PI(3,4,5)P3, the product of phosphatidylinositol 3-kinase (PI3K), accumulates locally at the leading edge. The key intermediate event that creates this strong PI(3,4,5)P3 asymmetry remains unclear. Here, we show that Ras is rapidly and transiently activated in response to chemoattractant stimulation and regulates PI3K activity. Ras activation occurs at the leading edge of chemotaxing cells, and this local activation is independent of the F-actin cytoskeleton, whereas PI3K localization is dependent on F-actin polymerization. Inhibition of Ras results in severe defects in directional movement, indicating that Ras is an upstream component of the cell's compass. These results support a mechanism by which localized Ras activation mediates leading edge formation through activation of basal PI3K present on the plasma membrane and other Ras effectors required for chemotaxis. A feedback loop, mediated through localized F-actin polymerization, recruits cytosolic PI3K to the leading edge to amplify the signal.

scholarly journals Ras activation and symmetry breaking during Dictyostelium chemotaxis

2013 ◽  
Vol 126 (19) ◽  
pp. 4502-4513 ◽  
Author(s):  
A. Kortholt ◽  
I. Keizer-Gunnink ◽  
R. Kataria ◽  
P. J. M. Van Haastert
Keyword(s):  
Symmetry Breaking ◽  
Ras Activation

scholarly journals Identification of a new regulation pathway of EGFR and E-cadherin dynamics

2020 ◽  
Author(s):  
Veronique Proux-Gillardeaux ◽  
Tamara Advedissian ◽  
Charlotte Perin ◽  
Jean-Christophe Gelly ◽  
Mireille Viguier ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Direct Interaction ◽  
Endocytic Pathway ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Epithelial Homeostasis ◽  
Proliferation And Differentiation ◽  
E Cadherin

ABSTRACTEGFR plays key roles in multiple cellular processes such as cell differentiation, cell proliferation, migration and epithelia homeostasis. Phosphorylation of the receptor, intracellular signaling and trafficking are major events regulating EGFR functions. Galectin-7, a soluble lectin expressed in epithelia such as the skin, has been shown to be involved in cell differentiation. Through this study we demonstrate that galectin-7 regulates EGFR function by a direct interaction with its extracellular domain hence modifying its downstream signaling and endocytic pathway. From observations in mice we focused on the molecular mechanisms deciphering the glycosylation dependent interaction between EGFR and galectin-7. Interestingly, we also revealed that galectin-7 is a direct binder of both EGFR and E-cadherin bridging them together. Strikingly this study not only deciphers a new molecular mechanism of EGFR regulation but also points out a novel molecular interaction between EGFR and E-cadherin, two major regulators of the balance between proliferation and differentiation.SUMMARYEGFR and E-cadherin are known to interact and to regulate epithelial homeostasis. In this study we unravel in the epidermis a new partner and regulator of EGFR which also binds E-cadherin reciprocally bridging their dynamics and functions.

scholarly journals Pattern-induced local symmetry breaking in active-matter systems

2020 ◽  
Vol 117 (50) ◽  
pp. 31623-31630
Author(s):  
Jonas Denk ◽  
Erwin Frey
Keyword(s):  
Symmetry Breaking ◽  
Biological Systems ◽  
Local Symmetry ◽  
Theoretical Explanation ◽  
Feedback Mechanism ◽  
Hydrodynamic Theory ◽  
Active Matter ◽  
Theoretical Understanding ◽  
Self Organized ◽  
Microscopic Interactions

The emergence of macroscopic order and patterns is a central paradigm in systems of (self-)propelled agents and a key component in the structuring of many biological systems. The relationships between the ordering process and the underlying microscopic interactions have been extensively explored both experimentally and theoretically. While emerging patterns often show one specific symmetry (e.g., nematic lane patterns or polarized traveling flocks), depending on the symmetry of the alignment interactions patterns with different symmetries can apparently coexist. Indeed, recent experiments with an actomysin motility assay suggest that polar and nematic patterns of actin filaments can interact and dynamically transform into each other. However, theoretical understanding of the mechanism responsible remains elusive. Here, we present a kinetic approach complemented by a hydrodynamic theory for agents with mixed alignment symmetries, which captures the experimentally observed phenomenology and provides a theoretical explanation for the coexistence and interaction of patterns with different symmetries. We show that local, pattern-induced symmetry breaking can account for dynamically coexisting patterns with different symmetries. Specifically, in a regime with moderate densities and a weak polar bias in the alignment interaction, nematic bands show a local symmetry-breaking instability within their high-density core region, which induces the formation of polar waves along the bands. These instabilities eventually result in a self-organized system of nematic bands and polar waves that dynamically transform into each other. Our study reveals a mutual feedback mechanism between pattern formation and local symmetry breaking in active matter that has interesting consequences for structure formation in biological systems.

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