Distributing tasks via multiple input pathways increases cellular survival in stress

Granados, Alejandro A; Crane, Matthew M.; Montaño-Gutierrez, Luis Fernando; Tanaka, Reiko; Voliotis, Margaritis; Swain, Peter S.

doi:10.7554/elife.21415

Cited by 52 publications

(71 citation statements)

References 63 publications

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“…The degree of maximum nuclear enrichment was virtually indistinguishable in both strains, suggesting that the mutant maintains the ability to sense and respond to acute osmotic shock. In the WT strain, Hog1 exited the nucleus and its cytoplasmic levels adapted to the pre-stimulus values within 45 minutes on average, consistent with previous reports 20 . Surprisingly, however, the return of Hog1 to the cytoplasm was much faster in the sic1Δ cells, occurring on average within 33 minutes ( Figure 1C).…”

Section: Removal Of Hog1-mediated Cell Cycle Arrest Accelerates Adaptsupporting

confidence: 91%

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Stress-Induced Transient Cell Cycle Arrest Coordinates Metabolic Resource Allocation to Balance Adaptive Tradeoffs

Kochanowski

Diether

et al. 2020

Preprint

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The ability of a cell to mount a robust response to an environmental perturbation is paramount to its survival. While cells deploy a spectrum of specialized counter-measures to deal with stress, a near constant feature of these responses is a down regulation or arrest of the cell cycle. It has been widely assumed that this modulation of the cell cycle is instrumental in facilitating a timely response towards cellular adaptation. Here, we investigate the role of cell cycle arrest in the hyperosmotic shock response of the model organism S. cerevisiae by deleting the osmoshock-stabilized cell cycle inhibitor Sic1, thus enabling concurrent stress response activation and cell cycle progression. Contrary to expectation, we found that removal of stress-induced cell cycle arrest accelerated the adaptive response to osmotic shock instead of delaying it. Using a combination of time-lapse microscopy, genetic perturbations and quantitative mass spectrometry, we discovered that unabated cell cycle progression during stress enables the liquidation of internal glycogen stores, which are then shunted into the osmotic shock response to fuel a faster adaptation. Therefore, osmo-adaptation in wild type cells is delayed because cell cycle arrest diminishes the ability of the cell to tap its glycogen stores. However, acceleration of osmo-adaptation in mutant cells that do not arrest comes at the cost of acute sensitivity to a subsequent osmo-stress. This indicates that despite the ostensible advantage faster adaptation poses, there is a trade-off between the short-term benefit of faster adaptation and the vulnerability it poses to subsequent insults. We suggest that cell cycle arrest acts as a carbon flux valve to regulate the amount of material that is devoted to osmotic shock, balancing short term adaptation with long-term robustness.

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Section: Removal Of Hog1-mediated Cell Cycle Arrest Accelerates Adaptsupporting

confidence: 91%

“…Volume restoration and exit of Hog1 from the nucleus also coincides with resumption of cell cycle progression 18 . The adaptive translocation pattern of Hog1 has been the subject of many studies for its robust, reproducible and stereotyped pattern, which acts as a real-time reporter of hyperosmotic stress adaptation 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Stress-Induced Transient Cell Cycle Arrest Coordinates Metabolic Resource Allocation to Balance Adaptive Tradeoffs

Kochanowski

Diether

et al. 2020

Preprint

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“…We do know that the biochemical implementation of such representations is likely to be substantially stochastic (11) and that the same biochemistry may be used to sense disparate environments. Furthermore, cells typically have just 'one shot' at mounting the appropriate response from these internal representations, with competition being unforgiving for those that delay, at least among microbes (12)(13)(14). Here we use information theory to investigate how eukaryotic cells answer these challenges through their internal organization of extracellular information.…”

Section: Significance Statementmentioning

confidence: 99%

Distributed and dynamic intracellular organization of extracellular information

Granados

Pietsch²,

Cepeda-Humerez

et al. 2017

Preprint

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Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for ten transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: generalists (Msn2/4, Tod6/Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. Each transcription factor reports differently, and it is only their collective response that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change, and we predict that such multi-dimensional representations are common in cellular decision-making. Significance StatementTo thrive in diverse environments, cells must represent extracellular change intracellularly despite stochastic biochemistry. Here we introduce a quantitative framework for investigating the organization of information within a cell. Combining single-cell measurements of intracellular dynamics with a new, scalable methodology for estimating mutual information between time-series and a discrete input, we demonstrate that extracellular information is encoded in the dynamics of the nuclear localization of transcription factors and that information is lost with alternative static statistics. Any one transcription factor is usually insufficient, but the collective dynamics of multiple transcription factors can represent complex extracellular change. We therefore show that a cell's internal representation of its environment can be both distributed across diverse proteins and dynamically encoded.

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“…It has been shown previously that different temporal patterns of stresses can be used to probe signaling pathways to identify pathway models [14,18], to probe pathway dynamic properties [22], to hyperactivate a pathway [23] or to assign biological function to pathway branches [24,25]. In all of these cases rapidly changing environments activate Hog1 kinase robustly, resulting in strong gene expression response and an increase in glycerol levels that enable the cells to survive extracellular stress ( Figure 4E, left panel).…”

Section: Discussionmentioning

confidence: 87%

A rate threshold mechanism regulates MAPK stress signaling and survival

Johnson

Jashnsaz

et al. 2017

Preprint

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A hallmark of cellular stress response pathways is to protect cells from different environmental insults. While much is known about how cells are protected against acute stresses of different types, the mechanisms underpinning how cells are protected against gradually changing stresses are poorly understood. Here we demonstrate that a linear stress gradient but not a step, pulse or a quadratic gradient of the same stressor and intensity causes a severe cell growth phenotype. We determined that this phenotype is caused by the failure of cells to activate the stress-activated protein kinase signaling pathway due to a threshold in the rate of stress application. This lack of response occurs despite cells physically detecting the relatively slow changes in stress signal.These findings have fundamental implications for understanding mechanisms of how temporally changing environments impact biological phenotype.

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Distributing tasks via multiple input pathways increases cellular survival in stress

Cited by 52 publications

References 63 publications

Stress-Induced Transient Cell Cycle Arrest Coordinates Metabolic Resource Allocation to Balance Adaptive Tradeoffs

Stress-Induced Transient Cell Cycle Arrest Coordinates Metabolic Resource Allocation to Balance Adaptive Tradeoffs

Distributed and dynamic intracellular organization of extracellular information

A rate threshold mechanism regulates MAPK stress signaling and survival

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