Using Optogenetics to Interrogate the Dynamic Control of Signal Transmission by the Ras/Erk Module

Toettcher, Jared E.; Weiner, Orion D.; Lim, Wendell A.

doi:10.1016/j.cell.2013.11.004

Cited by 479 publications

(567 citation statements)

References 49 publications

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“…Thus, it is important to measure the time schedules in signaling cascades to understand the gene expression dynamics. A recent optogenetic approach revealed the transmission delay in the ERK-Ras signaling pathway by combining singlenode-specific optogenetic perturbation (opto-SOS) with fluorescence reporters that monitor localizations of two molecular components: SOS and ERK (Toettcher et al 2013). However, such desirable pairs of node-specific reporters are not always available, especially in the DeltaNotch signaling pathway.…”

Section: Identification Of Time Schedules In Signaling Cascadesmentioning

confidence: 99%

Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information

et al. 2017

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Cells communicate with each other to coordinate their gene activities at the population level through signaling pathways. It has been shown that many gene activities are oscillatory and that the frequency and phase of oscillatory gene expression encode various types of information. However, whether or how such oscillatory information is transmitted from cell to cell remains unknown. Here, we developed an integrated approach that combines optogenetic perturbations and single-cell bioluminescence imaging to visualize and reconstitute synchronized oscillatory gene expression in signal-sending and signal-receiving processes. We found that intracellular and intercellular periodic inputs of Notch signaling entrain intrinsic oscillations by frequency tuning and phase shifting at the singlecell level. In this way, the oscillation dynamics are transmitted through Notch signaling, thereby synchronizing the population of oscillators. Thus, this approach enabled us to control and monitor dynamic cell-to-cell transfer of oscillatory information to coordinate gene expression patterns at the population level.

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Section: Identification Of Time Schedules In Signaling Cascadesmentioning

confidence: 99%

Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information

et al. 2017

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“…2); however, the functional importance of this interaction has yet to be determined (Fujimori et al, 2004). Interestingly, the APB domain of PIF6 and PIF3 along with the N-terminal domain of phyB have been used to develop a light-switchable gene regulatory module for studying cellular signaling pathways in metazoans (Shimizu-Sato et al, 2002;Levskaya et al, 2009;Toettcher et al, 2011aToettcher et al, , 2011bToettcher et al, , 2013.…”

Section: Distinct and Shared Biological Functions Of Pifs In Arabidopsismentioning

confidence: 99%

Phytochromes and Phytochrome Interacting Factors

2017

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The basic helix-loop-helix domain-containing transcription factors that interact physically with the red and far-red light photoreceptors, phytochromes, are called PHYTOCHROME INTERACTING FACTORS (PIFs). In the last two decades, the phytochrome-PIF signaling module has been shown to be conserved from Physcomitrella patens to higher plants. Exciting recent studies highlight the discovery of at least four distinct kinases (PPKs, CK2, BIN2, and phytochrome itself) and four families of ubiquitin ligases (SCF EBF 1/2 , CUL3 LRB , CUL3 BOP , and CUL4 COP1-SPA ) that regulate PIF abundance both in dark and light conditions. This review discusses these recent discoveries with a focus on the central phytochrome signaling mechanisms that have a profound impact on plant growth and development in response to light.

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“…Signaling pathways also differ in the level of response to a stimulus. Some exhibit graded (or analog) outputs (Toettcher et al, 2013), whereas others show all-or-none (or digital) responses (Tay et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Akt signaling dynamics in individual cells

Gross

Rotwein

2015

Journal of Cell Science

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The protein kinase Akt (for which there are three isoforms) is a key intracellular mediator of many biological processes, yet knowledge of Akt signaling dynamics is limited. Here, we have constructed a fluorescent reporter molecule in a lentiviral delivery system to assess Akt kinase activity at the single cell level. The reporter, a fusion between a modified FoxO1 transcription factor and clover, a green fluorescent protein, rapidly translocates from the nucleus to the cytoplasm in response to Akt stimulation. Because of its long half-life and the intensity of clover fluorescence, the sensor provides a robust readout that can be tracked for days under a range of biological conditions. Using this reporter, we find that stimulation of Akt activity by IGF-I is encoded into stable and reproducible analog responses at the population level, but that single cell signaling outcomes are variable. This reporter, which provides a simple and dynamic measure of Akt activity, should be compatible with many cell types and experimental platforms, and thus opens the door to new insights into how Akt regulates its biological responses.

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Using Optogenetics to Interrogate the Dynamic Control of Signal Transmission by the Ras/Erk Module

Cited by 479 publications

References 49 publications

Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information

Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information

Phytochromes and Phytochrome Interacting Factors

Akt signaling dynamics in individual cells

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