Stochastic ERK Activation Induced by Noise and Cell-to-Cell Propagation Regulates Cell Density-Dependent Proliferation

Aoki, Kazuhiro; Kumagai, Yuka; Sakurai, Atsuro; Komatsu, Naoki; Fujita, Yoshihisa; Shionyu, Clara; Matsuda, Minoru

doi:10.1016/j.molcel.2013.09.015

Cited by 310 publications

(378 citation statements)

References 54 publications

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“…Currently, several lightinduced dimerization (LID) systems, in which photoactivatable proteins are dimerized by light in a reversible manner, are available. Among them, the cryptochrome 2 (CRY2) and cryptochrome-interacting basic helix-loop-helix1 (CIB1) pair has been widely used to control cell signaling through its lightinduced heterodimerization (11)(12)(13). CRY2 associates with its binding partner CIB1 upon exposure to blue light within a few seconds, and the complex is dissociated under a dark condition within several minutes (14).…”

mentioning

confidence: 99%

Efficient synthesis of phycocyanobilin in mammalian cells for optogenetic control of cell signaling

Uda

Goto

Oda

et al. 2017

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

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114

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Optogenetics is a powerful tool to precisely manipulate cell signaling in space and time. For example, protein activity can be regulated by several light-induced dimerization (LID) systems. Among them, the phytochrome B (PhyB)–phytochrome-interacting factor (PIF) system is the only available LID system controlled by red and far-red lights. However, the PhyB–PIF system requires phycocyanobilin (PCB) or phytochromobilin as a chromophore, which must be artificially added to mammalian cells. Here, we report an expression vector that coexpresses HO1 and PcyA with Ferredoxin and Ferredoxin-NADP+ reductase for the efficient synthesis of PCB in the mitochondria of mammalian cells. An even higher intracellular PCB concentration was achieved by the depletion of biliverdin reductase A, which degrades PCB. The PCB synthesis and PhyB–PIF systems allowed us to optogenetically regulate intracellular signaling without any external supply of chromophores. Thus, we have provided a practical method for developing a fully genetically encoded PhyB–PIF system, which paves the way for its application to a living animal.

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mentioning

confidence: 99%

Efficient synthesis of phycocyanobilin in mammalian cells for optogenetic control of cell signaling

Uda

Goto

Oda

et al. 2017

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

Self Cite

114

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“…It was reported that rat kidney epithelial cells show stochastically pulsed MAPK activation in vitro, the frequency of which correlates with cell proliferation rate (Aoki et al, 2013). Interestingly, this pulsed MAPK activity is propagated to neighbor cells through EGF/ Ras/MAPK signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…A similar propagation mechanism of cell proliferation may underlie clustering of cell division in zebrafish lens epithelium. Given that the frequency of MAPK activity pulses depends on cell density (Aoki et al, 2013), it would be interesting to investigate whether the level of cell proliferation depends on epithelial tension. Epithelial tension is transmitted through adherens junctions via E-cadherin (Borghi et al, 2012;Yonemura et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Cell division and cadherin-mediated adhesion regulate lens epithelial cell movement in zebrafish

Mochizuki¹,

Luo²,

Tsai³

et al. 2017

Journal of Cell Science

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In vertebrates, lens epithelial cells cover the anterior half of the lens fiber core. During development, lens epithelial cells proliferate, move posteriorly and differentiate into lens fiber cells after passing through the equator. To elucidate the mechanisms underlying lens epithelial cell movement, we conducted time-lapse imaging of zebrafish lens epithelium. Lens epithelial cells do not intermingle but maintain their relative positions during development. Cell division induces epithelial rearrangement, which subsequently promotes cell movement towards the equator. These data suggest that cell division is the major driving force for cell movement. In zebrafish, E-cadherin is expressed in lens epithelium, whereas N-cadherin is required for lens fiber growth. E-cadherin reduced lens epithelial cell movement, whereas N-cadherin enhanced it. Laser ablation experiments revealed that lens epithelium is governed by pulling tension, which is modulated by these cadherins. Thus, cell division and cadherinmediated adhesion regulate lens epithelial cell movement via modulation of epithelial tension.

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“…With this system, the construct between inverted terminal repeat sequences is randomly inserted into a host genome as a single structure by cotransfection with a DNA coding the specific transposase. Using this method, we have effectively obtained stable cell lines that express sufficient amounts of FRET biosensors (32,33), and to date we have not experienced any problems related to the recombination or destruction of the constructs.…”

Section: Generation Of Stable Cell Lines and Transgenic Mice Expressimentioning

confidence: 99%

Future Perspective of Single-Molecule FRET Biosensors and Intravital FRET Microscopy

Hirata

Kiyokawa

2016

Biophysical Journal

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Fö rster (or fluorescence) resonance energy transfer (FRET) is a nonradiative energy transfer process between two fluorophores located in close proximity to each other. To date, a variety of biosensors based on the principle of FRET have been developed to monitor the activity of kinases, proteases, GTPases or lipid concentration in living cells. In addition, generation of biosensors that can monitor physical stresses such as mechanical power, heat, or electric/magnetic fields is also expected based on recent discoveries on the effects of these stressors on cell behavior. These biosensors can now be stably expressed in cells and mice by transposon technologies. In addition, two-photon excitation microscopy can be used to detect the activities or concentrations of bioactive molecules in vivo. In the future, more sophisticated techniques for image acquisition and quantitative analysis will be needed to obtain more precise FRET signals in spatiotemporal dimensions. Improvement of tissue/organ position fixation methods for mouse imaging is the first step toward effective image acquisition. Progress in the development of fluorescent proteins that can be excited with longer wavelength should be applied to FRET biosensors to obtain deeper structures. The development of computational programs that can separately quantify signals from single cells embedded in complicated three-dimensional environments is also expected. Along with the progress in these methodologies, two-photon excitation intravital FRET microscopy will be a powerful and valuable tool for the comprehensive understanding of biomedical phenomena.Since the discovery of green fluorescent protein (GFP) (1), scientists have been widely employing this gene-encoded fluorescent protein (FP) to investigate the spatiotemporal dynamics of molecules with subcellular resolution. One of the applications of FP engineering is the development of biosensors based on the principle of Förster (or fluorescence) resonance energy transfer (FRET) (2). FRET is a nonradiative energy transfer process between two fluorophores located in close proximity to each other, and its efficiency is strongly dependent on the distance between the fluorophores. More precisely, the energy transfer rate (k t ) from a donor to an acceptor fluorophore is calculated in the following Förster's equation;where J is the overlap of donor emission and acceptor excitation spectra, k 2 is an orientation factor of transition moment (a factor determined by the relative orientation of the two fluorophores), n is a refractive index, R is the distance between the donor and acceptor fluorophores, and k f is the donor fluorescence emission speed. Therefore, FRET efficiency is determined by the distance and orientation of the two fluorophores. To measure FRET efficiency, there are roughly two methods; ratiometric analysis and lifetime analysis. Ratiometric analysis utilizes fluorescence intensity of an acceptor (e.g., yellow FP (YFP)) and a donor (e.g., cyan FP (CFP)) upon the donor excitation. Because accept...

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Stochastic ERK Activation Induced by Noise and Cell-to-Cell Propagation Regulates Cell Density-Dependent Proliferation

Cited by 310 publications

References 54 publications

Efficient synthesis of phycocyanobilin in mammalian cells for optogenetic control of cell signaling

Efficient synthesis of phycocyanobilin in mammalian cells for optogenetic control of cell signaling

Cell division and cadherin-mediated adhesion regulate lens epithelial cell movement in zebrafish

Future Perspective of Single-Molecule FRET Biosensors and Intravital FRET Microscopy

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