Light-based feedback for controlling intracellular signaling dynamics

Jared E. Toettcher; Delquin Gong; Wendell A. Lim; Orion D. Weiner

doi:10.1038/nmeth.1700

Light-based feedback for controlling intracellular signaling dynamics

Jared E. Toettcher
, Delquin Gong
, Wendell A. Lim
, Orion D. Weiner

Research output: Contribution to journal › Article › peer-review

238 Scopus citations

Abstract

The ability to apply precise inputs to signaling species in live cells would be transformative for interrogating and understanding complex cell-signaling systems. Here we report an 'optogenetic' method for applying custom signaling inputs using feedback control of a light-gated protein-protein interaction. We applied this strategy to perturb protein localization and phosphoinositide 3-kinase activity, generating time-varying signals and clamping signals to buffer against cell-to-cell variability or changes in pathway activity.

Original language	English (US)
Pages (from-to)	837-839
Number of pages	3
Journal	Nature Methods
Volume	8
Issue number	10
DOIs	https://doi.org/10.1038/nmeth.1700
State	Published - Oct 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biotechnology
Biochemistry
Molecular Biology
Cell Biology

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10.1038/nmeth.1700

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@article{87061470cb89472795ce79dbfe2d9c65,

title = "Light-based feedback for controlling intracellular signaling dynamics",

abstract = "The ability to apply precise inputs to signaling species in live cells would be transformative for interrogating and understanding complex cell-signaling systems. Here we report an 'optogenetic' method for applying custom signaling inputs using feedback control of a light-gated protein-protein interaction. We applied this strategy to perturb protein localization and phosphoinositide 3-kinase activity, generating time-varying signals and clamping signals to buffer against cell-to-cell variability or changes in pathway activity.",

author = "Toettcher, \{Jared E.\} and Delquin Gong and Lim, \{Wendell A.\} and Weiner, \{Orion D.\}",

note = "Funding Information: We thank all members of the Weiner and Lim laboratories, A. Levskaya, A. Edelstein and N. Stuurman for helpful comments and discussions, and A. Loewer and H. El-Samad for critically reading this manuscript. TagBFP construct was a gift from members of the Vale lab (University of California San Francisco), pHR lentiviral vectors were provided by J.R. James (University of California San Francisco), and the iSH construct was a gift from members of the Meyer lab (Stanford University). This work was supported by a Cancer Research Institute Postdoctoral Fellowship to J.E.T., an American Cancer Society postdoctoral fellowship to D.G., the Howard Hughes Medical Institute and US National Institutes of Health grants GM55040, GM62583, EY016546 and P50GM081879 to W.A.L., and a National Institutes of Health grant GM084040 and a Searle Scholars Fellowship to O.D.W.",

year = "2011",

month = oct,

doi = "10.1038/nmeth.1700",

language = "English (US)",

volume = "8",

pages = "837--839",

journal = "Nature Methods",

issn = "1548-7091",

publisher = "Nature Research",

number = "10",

}

TY - JOUR

T1 - Light-based feedback for controlling intracellular signaling dynamics

AU - Toettcher, Jared E.

AU - Gong, Delquin

AU - Lim, Wendell A.

AU - Weiner, Orion D.

N1 - Funding Information: We thank all members of the Weiner and Lim laboratories, A. Levskaya, A. Edelstein and N. Stuurman for helpful comments and discussions, and A. Loewer and H. El-Samad for critically reading this manuscript. TagBFP construct was a gift from members of the Vale lab (University of California San Francisco), pHR lentiviral vectors were provided by J.R. James (University of California San Francisco), and the iSH construct was a gift from members of the Meyer lab (Stanford University). This work was supported by a Cancer Research Institute Postdoctoral Fellowship to J.E.T., an American Cancer Society postdoctoral fellowship to D.G., the Howard Hughes Medical Institute and US National Institutes of Health grants GM55040, GM62583, EY016546 and P50GM081879 to W.A.L., and a National Institutes of Health grant GM084040 and a Searle Scholars Fellowship to O.D.W.

PY - 2011/10

Y1 - 2011/10

N2 - The ability to apply precise inputs to signaling species in live cells would be transformative for interrogating and understanding complex cell-signaling systems. Here we report an 'optogenetic' method for applying custom signaling inputs using feedback control of a light-gated protein-protein interaction. We applied this strategy to perturb protein localization and phosphoinositide 3-kinase activity, generating time-varying signals and clamping signals to buffer against cell-to-cell variability or changes in pathway activity.

AB - The ability to apply precise inputs to signaling species in live cells would be transformative for interrogating and understanding complex cell-signaling systems. Here we report an 'optogenetic' method for applying custom signaling inputs using feedback control of a light-gated protein-protein interaction. We applied this strategy to perturb protein localization and phosphoinositide 3-kinase activity, generating time-varying signals and clamping signals to buffer against cell-to-cell variability or changes in pathway activity.

UR - https://www.scopus.com/pages/publications/80053347082

UR - https://www.scopus.com/pages/publications/80053347082#tab=citedBy

U2 - 10.1038/nmeth.1700

DO - 10.1038/nmeth.1700

M3 - Article

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AN - SCOPUS:80053347082

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VL - 8

SP - 837

EP - 839

JO - Nature Methods

JF - Nature Methods

IS - 10

ER -

Light-based feedback for controlling intracellular signaling dynamics

Abstract

All Science Journal Classification (ASJC) codes

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