Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling

Maeder, Céline I.; Hink, Mark A.; Kinkhabwala, Ali; Mayr, Reinhard; Bastiaens, Philippe I. H.; Knop, Michael

doi:10.1038/ncb1652

Cited by 222 publications

(228 citation statements)

References 31 publications

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“…The high contribution (48%) can be explained taking the presence of non-matured mCherry into account. Maeder and co-workers used a similar construct with a different linker in yeast and found that 50% of mCherry is not matured (Maeder et al 2007). Non-matured mCherry contains green chromophores, which are different from EGFP and with shorter fluorescence lifetimes (Cotlet et al 2001).…”

Section: Resultsmentioning

confidence: 99%

Time-resolved FRET fluorescence spectroscopy of visible fluorescent protein pairs

et al. 2009

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Section: Resultsmentioning

confidence: 99%

Time-resolved FRET fluorescence spectroscopy of visible fluorescent protein pairs

et al. 2009

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“…Spatial gradients of protein activities organize signaling around cellular structures, such as membranes, chromosomes and scaffolds, and provide positional cues for key processes, including cell division. Such intracellular gradients of protein activities have been detected in live cells using imaging technologies based on fluorescence resonance energy (Maeder et al 2007). …”

Section: Spatial Signal Propagationmentioning

confidence: 99%

Complexity of Receptor Tyrosine Kinase Signal Processing

Volinsky

Kholodenko

2013

Cold Spring Harbor Perspectives in Biology

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Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the immediate posttranslational and delayed transcriptional controls by multiple feed forward and feedback loops together with pathway cross talk, adapt cells to the combinatorial variety of external cues and conditions. This intricate network circuitry endows cells with emerging capabilities for RTK signal processing and decoding. We illustrate how mathematical modeling facilitates our understanding of RTK network behaviors by unraveling specific systems properties, including bistability, oscillations, excitable responses, and generation of intricate landscapes of signaling activities.

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“…This lack of temporal resolution prevented to investigate whether mitochondrial permeabilization is subject to spatial coordination by processes such as localized production of signaling molecules and/or diffusion, which were previously described as important regulators of other cellular signaling pathways, such as the forwarding of phosphorylation signals and Ca 2 þ waves. [15][16][17] We here describe a novel approach combining rapid cellular imaging and computational modeling to remedy this limitation in the analysis of apoptotic signaling. Taking advantage of the synchrony of sibling cells in apoptosis onset, we established an imaging technique that is capable of predicting the time of MOMP for individual cells with high probability.…”

mentioning

confidence: 99%

Dynamics of outer mitochondrial membrane permeabilization during apoptosis

et al. 2009

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Individual cells within a population undergo apoptosis at distinct, apparently random time points. By analyzing cellular mitotic history, we identified that sibling HeLa cell pairs, in contrast to random cell pairs, underwent apoptosis synchronously. This allowed us to use high-speed cellular imaging to investigate mitochondrial outer membrane permeabilization (MOMP), a highly coordinated, rapid process during apoptosis, at a temporal resolution approximately 100 times higher than possible previously. We obtained new functional and mechanistic insight into the process of MOMP: We were able to determine the kinetics of pore formation in the outer mitochondrial membrane from the initiation phase of cytochrome-c-GFP redistribution, and showed differential pore formation kinetics in response to intrinsic or extrinsic apoptotic stimuli (staurosporine, tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL)). We also detected that the onset of mitochondrial permeabilization frequently proceeded as a wave through the cytosol, and that the frequency of wave occurrence in response to TRAIL was reduced by inhibition of protein kinase CK2. Computational analysis by a partial differential equation model suggested that the spread of permeabilization signals could sufficiently be explained by diffusion-adsorption velocities of locally generated permeabilization inducers. Taken together, our study yielded the first comprehensive analysis of clonal cell-to-cell variability in apoptosis execution and allowed to visualize and explain the dynamics of MOMP in cells undergoing apoptosis. Apoptosis is an evolutionary conserved cell death process that is fundamental to remove superfluous and damaged cells from the bodies of multicellular organisms. Impaired or excessive apoptosis has repeatedly been implicated as a major contributor to proliferative and degenerative diseases. Initiated by BH-3-only proteins of the Bcl-2 protein family, mitochondrial outer membrane permeabilization (MOMP) and the subsequent activation of effector caspases are rapid key processes crucial for the efficient execution of apoptotic cell death.Previous single-cell imaging studies using fluorescently tagged proteins showed that MOMP results in the coordinate release of mitochondrial intermembrane space proteins, including cytochrome-c (cyt-c) and Smac/Diablo, into the cytosol. The release was suggested to occur synchronously throughout the cytosol and with very fast kinetics, which seemed independent of the type of the apoptotic stimulus used, and also independent of downstream effector caspase activity. [1][2][3][4][5] Cytosolic cyt-c induces the rapid formation of the large multiprotein apoptosome complex, caspase-9 activation and subsequent activation of effector caspases-3 and -7. 6,7 In parallel, cytosolic Smac neutralizes x-linked inhibitor of apoptosis protein, the key inhibitor of caspases-9, -3 and -7. 8 As long as all key components of the execution network are present, effector caspase activation proceeds as a rapid and kinetically largely i...

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Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling

Cited by 222 publications

References 31 publications

Time-resolved FRET fluorescence spectroscopy of visible fluorescent protein pairs

Time-resolved FRET fluorescence spectroscopy of visible fluorescent protein pairs

Complexity of Receptor Tyrosine Kinase Signal Processing

Dynamics of outer mitochondrial membrane permeabilization during apoptosis

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